Tasuku Honjo

Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes (2009)

Sabouri, Zahra, Okazaki, Il-mi, Shinkura, Reiko, Begum, Nasim, Nagaoka, Hitoshi, Tsuchimoto, Daisuke, ...

The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed...

Identification of QTLs that modify peripheral neuropathy in NOD.H2b-Pdcd1-/- mice (2009)

Jiang, Fang, Yoshida, Taku, Nakaki, Fumio, Terawaki, Seigo, Chikuma, Shunsuke, Kato, Yu, ...

The non-obese diabetic (NOD) mouse strain is prone to developing various autoimmune syndromes including type I diabetes mellitus (T1DM), sialadenitis, thyroiditis and pancreatitis. Although the...

Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2 (2008)

Riccio, Orbicia, Van Gijn, Marielle E, Bezdek, April C, Pellegrinet, Luca, Van Es, Johan H, Zimber-Strobl, Ursula, ...

The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice....

PD-1 and PD-1 ligands: from discovery to clinical application (2007)

Okazaki, Taku, Honjo, Tasuku

Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon...

Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function (2007)

Terawaki, Seigo, Tanaka, Yoshimasa, Nagakura, Tomokazu, Hayashi, Tamon, Shibayama, Shiro, Muroi, Kaori, ...

The negative co-stimulatory receptor, programmed cell death 1 (PD-1), is induced on activated T cells and delivers inhibitory signals upon engagement with its ligands PD-L1 and PD-L2, which are...

Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID (2006)

Wakae, Koshou, Magor, Brad G., Saunders, Holly, Nagaoka, Hitoshi, Kawamura, Akemi, Kinoshita, Kazuo, ...

Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies....

Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID (2005)

Wakae, Koshou, Magor, Brad G., Saunders, Holly, Nagaoka, Hitoshi, Kawamura, Akemi, Kinoshita, Kazuo, ...

Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies....

PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells (2005)

Iwai, Yoshiko, Terawaki, Seigo, Honjo, Tasuku

Since metastasis is the major cause of death for cancer patients, there is an urgent need to develop new therapies to control hematogenous dissemination of cancer cells. Previously we and others...

Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants (2004)

Krebs, Luke T., Shutter, John R., Tanigaki, Kenji, Honjo, Tasuku, Stark, Kevin L., Gridley, Thomas

The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand...

Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants (2004)

Krebs, Luke T., Shutter, John R., Tanigaki, Kenji, Honjo, Tasuku, Stark, Kevin L., Gridley, Thomas

The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand...

Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants (2004)

Krebs, Luke T., Shutter, John R., Tanigaki, Kenji, Honjo, Tasuku, Stark, Kevin L., Gridley, Thomas

The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand...

Functional Assessment of Self-Renewal Activity of Male Germline Stem Cells Following Cytotoxic Damage and Serial Transplantation1 (2003)

Mito Kanatsu-Shinohara, Shinya Toyokuni, Takeshi Morimoto, Shigeyuki Matsui, Tasuku Honjo, Takashi Shinohara

Spermatogenesis is dependent on a small population of stem cells. Although stem cells are believed to expand infinitely, there is little functional evidence regarding whether spermatogonial stem...

Allogeneic Offspring Produced by Male Germ Line Stem Cell Transplantation into Infertile Mouse Testis1 (2003)

Mito Kanatsu-Shinohara, Narumi Ogonuki, Kimiko Inoue, Atsuo Ogura, Shinya Toyokuni, Tasuku Honjo, ...

The testis is one of several immune-privileged organs and is known for its unique ability to support allogeneic or xenogeneic tissue transplants. We investigated the possibility of deriving offspring...

Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision (2002)

Han, Hua, Tanigaki, Kenji, Yamamoto, Norio, Kuroda, Kazuki, Yoshimoto, Momoko, Nakahata, Tatsutoshi, ...

The transcription factor recombination signal binding protein‐J (RBP‐J) functions immediately downstream of the cell surface receptor Notch and mediates transcriptional activation by the...

Palindromic but not G-rich sequences are targets of class switch recombination (2001)

Tashiro, Junko, Kinoshita, Kazuo, Honjo, Tasuku

In order to understand the specificity of sequences or structures recognized by a recombinase involved in class switch recombination (CSR), we examined the relative CSR efficiency of various switch...

The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription (2001)

Tani, Shoichi, Kurooka, Hisanori, Aoki, Tomokazu, Hashimoto, Nobuo, Honjo, Tasuku

The evolutionarily-conserved DNA-binding protein RBP-J directly interacts with the RAM domain and the ankyrin (ANK) repeats of the Notch intracellular region (RAMIC), and activates transcription of...

Studies on the Cell-Type Specific Expression of RBP-L, a RBP-J Family Member, by Replacement Insertion of {beta}-Galactosidase (1999)

Minoguchi, Shigeru, Ikeda, Toshlo, Itohara, Shigeyoshi, Okaichi, Hironari, Honjo, Tasuku

The RBP-L gene encodes a DNA binding protein that is structurally related to RBP-J, the mammalian homolog of Drosophila Suppressor of Hairless. Although the RBP-L protein binds the same DNA sequence...

Requirement of IL-5 for induction of autoimmune hemolytic anemia in anti-red blood cell autoantibody transgenic mice (1999)

Sakiyama, Toshio, Ikuta, Koichi, Nisitani, Sazuku, Takatsu, Kiyoshi, Honjo, Tasuku

IL-5, IL-10 and lipopolysaccharide (LPS) are known to activate B-1 cells in vivo in normal mice and anti-red blood cell autoantibody transgenic mice (HL mice). To assess the exact role of IL-5 in...

Induction of Bip mRNA upon Programmed Cell Death of Differentiated PC12 Cells as Well as Rat Sympathetic Neurons (1997)

Aoki, Tomokazu, Koike, Tatsuro, Nakano, Toru, Shibahara, Keiichi, Kondo, Shigeru, Kikuchi, Haruhiko, ...

We have found that expression of the Bip (immunoglobulin heavy chain binding protein)/ GRP78 (glucose regulated protein 78) gene is markedly enhanced specifically among the heat shock protein (HSP)...

Structure of the Mutant Fibrillin-1 Gene in the Tight Skin (TSK) Mouse (1997)

Bona, Constantin A., Murai, Chihiro, Casares, Sophia, Kasturi, Kuppuswamy, Nishimura, Hiroyuki, Honjo, Tasuku, ...

Mice carrying the tight skin (TSK) mutation harbors a 3.0-kb genomic duplication (exons 17–40) of the fibrillin-1 gene (Fbn-1) locatedon band F of chromosome 2 as TSK mutation. We cloned and...

Antigen receptor-mediated B cell death is blacked by signaling via CD72 or treatment with dextran sukfate and is defective in autoimmunity-prone mice (1996)

Nomura, Takashi, Han, Hua, Howard, Maureen C., Yaglta, Hideo, Yakura, Hidetaka, Honjo, Tasuku, ...

Mature B cells undergo programmed cell death when surface(s)IG is extensively multimerized. A signal that blocks death of B cells is thus required for activation of B cells in response to antigen...

Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes (1996)

Agata, Yasutoshi, Kawasaki, Akemi, Nishimura, Hiroyuki, Ishida, Yasumasa, Tsubat, Takeshi, Yagita, Hideo, ...

A mAb J43 has been produced against the product of the mouse PD-1 gene, a member of the Ig gene superfamily, which was previously isolated from an apoptosis-induced T cell hybridoma (2B4.11) by using...

Developmentally regulated expression of the PD-1 protein on the surface of double-negative(CD4-CD8-) thymocytes (1996)

Nishimura, Hiroyuki, Agata, Yasutoshi, Kawasaki, Akemi, Sato, Masaki, Imamura, Sadao, Minato, Nagahiro, ...

PD-1, a member of the Ig superfamily, was previously isolated from an apoptosis-induced T cell hybridoma 2B4.11 by subtractive hybridization. Expression of the PD-1 mRNA is restricted to thymus in...

Defects of somatic hypermutation and class switching in alymphoplasia (aly) mutant mice (1996)

Shinkura, Reiko, Matsuda, Fumihiko, Sakiyama, Toshio, Tsubata, Takeshi, Hial, Hiroshi, Paumen, Michael, ...

The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph nodes, Peyer's patches and well-defined lymphoid follicles in the spleen. We found that antibody responses are elicited,...

High frequency class switching of an lgM+ B lymphoma clone CH12F3 to lgA+ cells (1996)

Nakamura, Motonobu, Kondo, Shigeru, Sugai, Manabu, Nazarea, Martina, Imamura, Sadao, Honjo, Tasuku

We have developed an efficient in vitro class switching system using a subclone (CH12F3) of the lgM+ CH12.LX lymphoma cell line. CH12F3 cells switched from surface lgM+ cells to surface...

Lineage marker-negative lymphocyte precursors derived from embryonic stem cells in vitro differentiate into mature lymphocytes in vivo (1994)

Nisitani, Sazuku, Tsubata, Takeshi, Honjo, Tasuku

We induced differentiation of mouse embryonic stem (ES) cells into lymphold cells by culturing in methylcellulose, followed by the co-culture with a bone marrow stromal cell line ST2 In the presence...

Recognition sequence of a highly conserved DNA binding protein RBP-Jx (1994)

Tun, Tin, Hamaguchi, Yasushi, Matsunami, Norisada, Furukawa, Takahisa, Honjo, Tasuku, Kawaichi, Masashi

DNA binding specificity of the RBP-Jx protein was extensively examined. The mouse RBP-Jx protein was originally isolated as a nuclear protein binding to the Jx type V(D)J recombination signal...

Site-directed mutagenesis study on DNA binding regions of the mouse homologue of Suppressor of Hairless, RBP-Jx (1994)

Chung, Chung-Nam, Hamaguchi, Yasushi, Honjo, Tasuku, Kawaichi, Masashi

To map regions important for DNA binding of the mouse homologue of Suppressor of Hairless or RBPJx protein, mutated mouse RBP-Jx cDNAs were made by insertion of oligonucleotide linkers or base...

Pseudo-high-affinity IL-2 receptor and growth signal transduction in lymphocytes (1993)

Saito, Yuji, Nazarea, Martina, Honjo, Tasuku, Okumura, K.

We examined whether the psuedo-hlgh-affinity IL-2 receptor (IL-2R) could transduce a growth signal in lymphocytes. Since lymphocytes devoid of the I chain were not available, we employed functional...

Isolation of cDNA encoding a binding protein specific to 5'-phosphorylated single-stranded DNA with G-rich sequences (1993)

Mizuta, Tatsunobu-Ryushin, Fukita, Yosho, Miyoshi, Takashi, Shimizu, Akira, Honjo, Tasuku

We have isolated the cDNA encoding a binding protein to the sequence motif of the Immunoglobulin Sμ region by the southwestern method. The binding protein designated Sμbp-2 specifically binds to...

Biochemical and Immunological Characterization of the DNA Binding Protein (RBP-Jx) to Mouse Jx Recombination Signal Sequence (1992)

Hamaguchi, Yasushi, Yamamoto, Yoshiki, Iwanari, Hiroko, Maruyama, Shingo, Furukawa, Takahisa, Matsunami, Norisada, ...

We have investigated whether Jx recombination signal sequence (RS) binding protein (RBP-Jx) has any partial catalytic activities involved in the VDJ recombination reaction, such as cleavage,...

Characterization of the enhancer region for germline transcription of the gamma 3 constant region gene of human immunoglobulin (1991)

Kuze, Kogo, Shimizu, Akira, Honjo, Tasuku, Watanabe, T.

A constant region gene (C) of the immunoglobulin heavy chain can be transcribed as germline transcripts from a promoter located upstream of a switch region. We have studied the structure and function...

Regulated expression of immunoglobulin trans-mRNA consisting of the variable region of a transgenic {micro} chain and constant regions of endogenous isotypes (1991)

Han, Hua, Okamoto, Masaya, Honjo, Tasuku, Shimizu, Akira

Our previous work demonstrated that chimeric immunoglobulin mRNAs (trans-mRNAs) composed of a transgenic VHDJH region and endogenous CH sequences could be synthesized, most likely by a trans-splicing...

Comparison of protein tyrosine phosphorylation and morphological changes induced by IL-2 and IL-3 (1991)

Sabe, Hisataka, Kuno, Junko, Koromllas, Antonis, Saito, Yuji, Kinashi, Tatsuo, Ueda, Masamichi, ...

We constructed cell lines which can proliferate in response to IL-2 or IL-3 by introducing a wild-type and mutant forms of cDNAs encoding the human IL-2R p75 chain into an IL-3 dependent...

Deletion of human JK segments by site-specific recombination recognizing the conserved nonamer and heptamer sequences (1990)

Nakatani, Tomoyuki, Horigome, Kazuhiko, Nomura, Noriko, Kondo, Tetsuya, Ohtsuka, Hiroshi, Noguchi, Hiroshi, ...

Mapping and partial sequencing of the productive K chain genomic DNA of FK-001 demonstrated a 1.8-kb deletion including the JK2, JK3, JK4, and JK5 segments. This deletion occurred between the...

Stepwise formation of the high-affinity complex of the interleukin 2 receptor (1990)

Saito, Yuji, Ogura, Toshihiko, Kamio, Masanori, Sabe, Hisataka, Uchiyama, Takashi, Honjo, Tasuku, ...

The interleukin 2 receptor (IL-2R) is composed of at least two polypeptides—a 55 kd protein (the L chain, p55, or α chain) and a 75 kd protein (the H chain, p75 or β chain). The high-affinity...

Purification and characterization of a protein that binds to the recombination signal sequence of the immunoglobulin Jx segment (1989)

Hamaguchi, Yasushi, Matsunami, Norisada, Yamamoto, Yoshiki, Honjo, Tasuku

A protein that binds to the recombination signal sequence (RS) of the immunoglobulin Jx segment was purified almost to homogeneity from the nuclear extract of a murine pre-B cell line 38B9. A similar...

Post-transcriptional allelic exclusion of two functionally rearranged T cell receptor {alpha} genes (1989)

Furutani, Makoto, Yanagi, Yusuke, Fujisawa, Isao, Nakayama, Toshinori, Kishimoto, Hidehiro, Kulda, Kelsuke, ...

We cloned and sequenced T cell receptor (TCR) α and β chain cDNA from a λgt10 library obtained from a murine I-Ak autoreactive helper T cell clone MS202. Two types of cDNA clones for the α chain...

An interleukin-4-dependent precursor clone is an intermediate of the differentiation pathway from an interleukin-3-dependent precursor clone into myeloid cells as well as B lymphocytes (1989)

Kinashi, Tatsuo, Tashiro, Kel, Inaba, Kayo, Takeda, Toshio, Palacios, Ronald, Honjo, Tasuku, ...

An Interleukin-3-dependent progenitor clone LyD9 and its Interleukin-4-dependent derivative clone K-4 were shown to differentiate into myeloid cells as well as B lymphocytes by coculture with bone...

Effects of the deregulated expression of human interleukin-2 in transgenic mice (1989)

Ishida, Yasumasa, Nishi, Miyuki, Taguchl, Osamu, Inaba, Kayo, Minato, Nagahiro, Kawaichi, Masashi, ...

We constructed transgenic mice that carry the cDNA of human interleukin-2 (IL-2) under the control of the H-2Kd promoter. The IL-2 transgenic mice expressed human IL-2 mRNA in the thymus, spleen,...

Production of sterile transcripts of C{gamma} genes in an IgM-producing human neoplastic B cell line that switches to IgG-producing cells (1989)

Sideras, Paschalis, Mizuta, Tatsunobu-Ryushin, Kanamorl, Hiroshi, Suzuki, Noboru, Okamoto, Masaya, Kuze, Kogo, ...

A human neoplastic B cell line SSK41 that expresses IgM on its surface switches spontaneously to IgG-producing cells. The SSK41 line contains a single immunoglobulin heavy-chain locus, the constant...

Biased Expression of Variable Region Gene Families of the Immunoglobulin Heavy Chain in Autoimmune-Prone Mice (1988)

Yaoita, Yoshio, Takahashi, Masazumi, Azuma, Chihiro, Kanai, Yoshiyuki, Honjo, Tasuku

We have examined usage of variable region gene families of the immunoglobulin heavy chain (VH gene family) in spleens of MRL/MpJ-lpr/lpr (MRL/lpr), (NZB�NZW)F1, and BXSB mice by Northern analysis...

Cloning of cDNA for human T-cell replacing factor (interieukin-5) and comparison with the murine homologue (1986)

Azuma, Chihiro, Tanabe, Toshizumi, Konishi, Mikdo, Kinashi, Tatsuo, Noma, Takafumi, Matsuda, Fumihiko, ...

We have cloned cDNA for T-cell replacing factor (interleukln-5), which replaces T-cell helper function for normal B cells which secrete immunoglo-bulin, from human T cell leukemia line, ATL-2, using...

Preferential transcription of HTLV-I LTR in cell-free extracts of human T cells producing HTLV-I viral proteins (1986)

Matsunami, Norisada, Siomi, Haruhiko, Hatanaka, Masakazu, Yaoita, Yoshio, Honjo, Tasuku

The promoters of the adenovlrus 2 major late gene, the mouse β–globin gene, the mouse lmmunoglobulin VH gene and the LTR of the human T-lympho-tropic retrovirus type I were tested for their...

Nucleotide sequence of mouse IL-2 receptor cDNA and its comparison with the human IL-2 receptor sequence (1985)

Shimuzu, Akira, Kondo, Shigeru, Takeda, Shun-ichi, Yodoi, Junji, Ishida, Norio, Sabe, Hisataka, ...

We have cloned cDNA encoding the mouse interleukin-2(IL-2) receptor from a murine T cell line, CTLL using human IL-2 receptor cDNA as probe. COS 7 cells transfected with the cDNA expressed the...

Molecular cloning and structure of the human interleukin 2 receptor gene (1985)

Ishida, Norio, Kanamori, Hiroshi, Noma, Takafumi, Nikaido, Toshio, Sabe, Hisataka, Suzuki, Noboru, ...

We have cloned the IL-2 receptor gene from human genomic DNA libraries using IL-2 receptor cDNA as probe. The genomic DNA segments that hybridized with cDNA were subcloned in M13 phages and their...

Introduction of Mouse C{varepsilon} Genes into Cos-7 Cells and Fertilized Mouse Eggs (1985)

YAMAMURA, Ken-ichi, MIKI, Tetsuro, SUZUKI, Noboru, EBIHARA, Taeko, KAWAI, Kazuhiko, KUMAHARA, Yuichi, ...

A fragment of the cloned gene for the mouse Cϵ chain, coding for the first, second, third, and fourth domains, has been coupled to the SV40 promotor region (pSV2-mCϵ). About 50 copies of...

Rearranged immunoglobulin heavy chain variable region (VH) pseudogene that deletes the second complementarity-determining region (1984)

Takahashi, Naoki, Noma, Takahumi, Honjo, Tasuku

We have cloned two rearranged heavy chain variable region (VH) genes from the IgG-producing human cell line CESS. The VH gene, which is linked to the µ chain constant region (Cµ) gene, has two...

Isolation and characterization of endonuclease J: a sequence-specific endonuclease cleaving immunoglobulin genes (1984)

Kataoka, Tohru, Kondo, Sigeru, Nishi, Miyuki, Kodaira, Mieko, Honjo, Tasuku

An endonuclease activity which cleaves close to the recombination sites of the imnunoglobulin JK segments was found in extracts of chicken bursa of Fabricius and characterized after partial...

Introduction of Human {gamma}1 Immunoglobulin Genes into Fertilized Mouse Eggs (1984)

YAMAMURA, Ken-ichi, KIKUTANI, Hitoshi, TAKAHASHI, Naoki, TAGA, Tetsuya, AKIRA, Shizuo, KAWAI, Kazuhiko, ...

A rearranged human γ1 immunoglobulin gene was introduced into fertilized mouse eggs. The phage Ch4A-VCE-γ1 was constructed by ligating an EcoRI and BglII fragment of pBR322-CESSV(CE-l) containing...

Structure of the human immunoglobulin Cε2 gene, a truncated pseudogene: Implications for its evolutionary origin (1983)

Hisajima, Hiroshi, Nishida, Yasuyoshi, Nakai, Sumiko, Takahashi, Naoki, Ueda, Shintaro, Honjo, Tasuku

Cloning of the overlapping DNA fragments together with Southern hybridization experiments showed the organization of the human Cε and Cα gene cluster as 5'-Cε2-14 kilobases-Cα1- - - -Cε1-13...

The D-JH complex is an intermediate to the complete immunoglobulin beavy-chain V-region gene (1983)

Yaoita, Yoshio, Matsunami, Norisada, Yong Choi, Cha, Sugiyama, Haruo, Kishimoto, Tadamitsu, Honjo, Tasuku

We have examined the organization of the immunoglobulin JH segments in three clones derived from a single Abelson murine leukemia virus-transformed cell. Cloning and nucleotide sequence analyses of...

Common terminal repeats of the macronuclear DNA are absent from the micronuclear DNA in hypotrichous ciliate, Stylonychia pustulata (1983)

Oka, Yoshio, Honjo, Tasuku

Comparison of nucleotide sequences of a macronuclear DNA and its micronuclear counterpart of a hypotrichous ciliate, Stylonychia pustulata, demonstrates that common terminal repeats (C4A4) of the...

Molecular cloning and nucleotide sequencing of human immunoglobulin {euro} chain cDNA (1983)

Seno, Masaharu, Kurokawa, Tsutomu, Ono, Yoshitaka, Onda, Haruo, Sasada, Reiko, Lagarshi, Koichi, ...

DNA complementary to mRNA of human immunoglobulin E heavy chain (€ chain) isolated and purified from U266 cells has been synthesized and inserted into the PstI site of pBR322 by G-C tailing. This...

Expression of human immunoglobulin E {varepsilon} chain cDNA in E.coli (1983)

Kurokawa, Tsutornu, Seno, Masaharu, Sasada, Reiko, Ona, Yoshitaka, Onda, Haruo, Igarashi, Koichi, ...

Using the cDNA of human 1D6DC; chain, three expression plasmids that code directly the constant portion of the 1D6DC; chain (C1D6DC;l-C 1D6DC;4, C 1D6DC;2-C 1D6DC;C4 and C 1D6DC;3-C 1D6DC;4 domains)...

Immunoglobulin switch region-like sequences in Drosophila melanogaster (1982)

Sakoyama, Yasuhiko, Yaoita, Yoshio, Honjo, Tasuku

We found immunoglobulin switch (S) region-like sequences in DNAs of wide variety of organisms including sea urchin, yeast and Drosophila that do not produce immnoglobulins. DNA fragments carrying...

The complete nucleotide sequence of mouse immunoglobulin {gamma}2a gene and evolution of heavy chain genes: further evidence for intervening sequence-mediated domain transfer (1981)

Yamawaki-Kataoka, Yuriko, Miyata, Takashi, Honjo, Tasuku

We have determined the complete nucleotide sequence (1990 base pairs) of mouse immunoglobulin τ2a gene, and compared it with the sequences of other τ subclass genes so far sequenced, i.e. τi and...

Complete nucleotide sequence of mouse imunoglobulin {micro} gene and comparison with other immunoglobulin heavy chain genes (1980)

Kawakami, Toshiaki, Takahashi, Naoki, Honjo, Tasuku

We have determined the complete nucleotide sequence (2168 bases) of the immunoglobulin μ gene cloned from newborn mouse DNA. The cloned l3kh fragment contained the entire constant region gene...

Cloning of human immunoglobulin {micro} gene and comparison with mouse {micro} gene (1980)

Takahashi, Naoki, Nakai, Sumiko, Honjo, Tasuku

We have cloned a 12 kb DNA segment containing human μ gene and its flanking sequence from human fetal liver DNA library using mouse μ gene as a probe. Partial nucleotide sequence determination...

Purification of Immunoglobulin Heavy Chain Messenger RNA by Immunoprecipitation from the Mouse Myeloma Tumor, MOPC-31C (1977)

ONO, Masao, KONDO, Toshihiko, KAWAKAMI, Masaya, HONJO, Tasuku

Immunoglobulin heavy chain mRNA was purified from immunoprecipitated polysomes derived from the mouse myeloma tumor, MOPC-31C. The purified mRNA migrated predominantly as a single band upon...

Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1α (SDF-1α) and SDF-1β are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage

Shioda, Tatsuo, Kato, Hiroyuki, Ohnishi, Yukano, Tashiro, Kei, Ikegawa, Masaya, Nakayama, Emi E., ...

CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural substrates have not been identified...

The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription

Tani, Shoichi, Kurooka, Hisanori, Aoki, Tomokazu, Hashimoto, Nobuo, Honjo, Tasuku

The evolutionarily-conserved DNA-binding protein RBP-J directly interacts with the RAM domain and the ankyrin (ANK) repeats of the Notch intracellular region (RAMIC), and activates transcription of...

Conservation of the biochemical mechanisms of signal transduction among mammalian Notch family members

Mizutani, Tomohiko, Taniguchi, Yoshihito, Aoki, Tomokazu, Hashimoto, Nobuo, Honjo, Tasuku

Mouse Notch1, which plays an important role in cell fate determination in development, is proteolytically processed within its transmembrane domain by unidentified γ-secretase-like activity that...

A hallmark of active class switch recombination: Transcripts directed by I promoters on looped-out circular DNAs

Kinoshita, Kazuo, Harigai, Motoko, Fagarasan, Sidonia, Muramatsu, Masamichi, Honjo, Tasuku

To specify when and where Ig class switch recombination (CSR) takes place, a good molecular marker closely associated with active CSR is required. CSR is accompanied by deletion of circular DNA from...

Variable deletion and duplication at recombination junction ends: Implication for staggered double-strand cleavage in class-switch recombination

Chen, Xiaochuan, Kinoshita, Kazuo, Honjo, Tasuku

Immunoglobulin class-switch recombination (CSR) gives rise to looped-out circular DNA of a cleaved S segment, which is lost eventually after cell divisions. To understand the molecular mechanism of S...

PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine

Okazaki, Taku, Maeda, Akito, Nishimura, Hiroyuki, Kurosaki, Tomohiro, Honjo, Tasuku

PD-1 is an immunoreceptor that belongs to the immunoglobulin (Ig) superfamily and contains two tyrosine residues in the cytoplasmic region. Studies on PD-1-deficient mice have shown that PD-1 plays...

Functional Replacement of the Intracellular Region of the Notch1 Receptor by Epstein-Barr Virus Nuclear Antigen 2

Sakai, Takashi, Taniguchi, Yoshihito, Tamura, Kumiko, Minoguchi, Shigeru, Fukuhara, Takataro, Strobl, Lothar J., ...

The intracellular region (RAMIC) of the mouse Notch1 receptor interacts with RBP-J/CBF-1, which binds to the DNA sequence CGTGGGAA and suppresses differentiation by transcriptional activation of...

Identification of Notch1 as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

Yanagawa, Shin-ichi, Lee, Jong-Seo, Kakimi, Kazuhiro, Matsuda, Yukihiro, Honjo, Tasuku, Ishimoto, Akinori

In contrast to wild-type mouse mammary tumor virus (MMTV), the MMTV mutants with specific deletions in the U3 region of their long terminal repeats cause T-cell lymphomas. In 30% of T-cell lymphomas...

Intracisternal Type A Particle-Mediated Activation of the Notch4/int3 Gene in a Mouse Mammary Tumor: Generation of Truncated Notch4/int3 mRNAs by Retroviral Splicing Events

Lee, Jong-Seo, Haruna, Tatsuya, Ishimoto, Akinori, Honjo, Tasuku, Yanagawa, Shin-ichi

The int3 oncogene was discovered as a frequent target in mouse mammary tumor virus-induced mammary tumors and encodes the intracellular domain of a Notch4/int3 protein. In one spontaneous mammary...

LIM Protein KyoT2 Negatively Regulates Transcription by Association with the RBP-J DNA-Binding Protein

Taniguchi, Yoshihito, Furukawa, Takahisa, Tun, Tin, Han, Hua, Honjo, Tasuku

The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to...

Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice

Kanatsu-Shinohara, Mito, Ogura, Atsuo, Ikegawa, Masaya, Inoue, Kimiko, Ogonuki, Narumi, Tashiro, Kei, ...

Sertoli cells play a pivotal role in spermatogenesis through their interactions with germ cells. To set up a strategy for treating male infertility caused by Sertoli cell dysfunction, we developed a...

Notch receptor cleavage depends on but is not directly executed by presenilins

Taniguchi, Yoshihito, Karlström, Helena, Lundkvist, Johan, Mizutani, Tomohiko, Otaka, Akira, Vestling, Monica, ...

Notch receptors undergo three distinct proteolytic cleavages during maturation and activation. The third cleavage occurs within the plasma membrane and results in the release and translocation of the...

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade

Iwai, Yoshiko, Ishida, Masayoshi, Tanaka, Yoshimasa, Okazaki, Taku, Honjo, Tasuku, Minato, Nagahiro

PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands (PD-L) and is suggested to play a role in the maintenance...

De novo protein synthesis is required for the activation-induced cytidine deaminase function in class-switch recombination

Doi, Tomomitsu, Kinoshita, Kazuo, Ikegawa, Masaya, Muramatsu, Masamichi, Honjo, Tasuku

Activation-induced cytidine deaminase (AID) is required for class-switch recombination (CSR), somatic hypermutation, and gene conversion of Ig genes. Although AID has sequence similarity to an...

Recombination signal sequence-binding protein Jκ alters mesodermal cell fate decisions by suppressing cardiomyogenesis

Schroeder, Timm, Fraser, Stuart T., Ogawa, Minetaro, Nishikawa, Satomi, Oka, Chio, Bornkamm, Georg W., ...

The transcription factor recombination signal sequence-binding protein Jκ (RBP-J) is a key downstream element in the signaling pathway of all four mammalian Notch receptors that are critically...

RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells

Eto, Tomonori, Kinoshita, Kazuo, Yoshikawa, Kiyotsugu, Muramatsu, Masamichi, Honjo, Tasuku

Antibody diversification by somatic hypermutation, gene conversion, and class switch recombination is completely dependent on activation-induced cytidine deaminase (AID). A recent report showing...

Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1

Ito, Satomi, Nagaoka, Hitoshi, Shinkura, Reiko, Begum, Nasim, Muramatsu, Masamichi, Nakata, Mikiyo, ...

Activation-induced cytidine deaminase (AID) is a molecule central to initiating class switch recombination, somatic hypermutation, and gene conversion of Ig genes. However, its mechanism to initiate...

Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut

Suzuki, Keiichiro, Meek, Bob, Doi, Yasuko, Muramatsu, Masamichi, Chiba, Tsutomu, Honjo, Tasuku, ...

The mechanism to maintain homeostasis of the gut microbiota remains largely unknown despite its critical role in the body defense. In the intestines of mice with deficiency of activation-induced...

Structures of defective P transposable elements prevalent in natural Q and Q-derived M strains of Drosophila melanogaster

Sakoyama, Yasuhiko, Todo, Takeshi, Ishiwa-Chigusa, Sadao, Honjo, Tasuku, Kondo, Sohei

Several DNA sequences with homology to the complete 2.9-kilobase (kb) P element from a P strain in the United States were isolated and characterized from two Drosophila melanogaster strains collected...

The Organization and Diversity of Immunoglobulin Genes*

Leder, Philip, Honjo, Tasuku, Packman, Seymour, Swan, David, Nau, Marion, Norman, Barbara

We have used purified mouse immunoglobulin light chain mRNA and synthetic DNA which is complementary to it to assess the reiteration frequency of gene sequences corresponding to the κ constant...

De novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination

Begum, Nasim A., Kinoshita, Kazuo, Muramatsu, Masamichi, Nagaoka, Hitoshi, Shinkura, Reiko, Honjo, Tasuku

Activation-induced cytidine deaminase is required for the DNA cleavage step of Ig class switch recombination (CSR). However, its molecular mechanism is controversial. RNA-editing hypothesis...

Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants

Krebs, Luke T., Shutter, John R., Tanigaki, Kenji, Honjo, Tasuku, Stark, Kevin L., Gridley, Thomas

The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand...

DNA cleavage in immunoglobulin somatic hypermutation depends on de novo protein synthesis but not on uracil DNA glycosylase

Nagaoka, Hitoshi, Ito, Satomi, Muramatsu, Masamichi, Nakata, Mikiyo, Honjo, Tasuku

Activation-induced cytidine deaminase (AID) is required for the DNA cleavage step of Ig somatic hypermutation (SHM). However, its molecular mechanism is controversial. The RNA editing hypothesis...

Two distinctive pathways for recruitment of naïve and primed IgM+ B cells to the gut lamina propria

Suzuki, Keiichiro, Meek, Bob, Doi, Yasuko, Honjo, Tasuku, Fagarasan, Sidonia

Intestinal IgA+ B cells are generated from IgM+ B cells by in situ class switching in two separate gut microenvironments: organized follicular structures and lamina propria (LP). However, the origin...

A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression

Kotani, Ai, Okazaki, Il-mi, Muramatsu, Masamichi, Kinoshita, Kazuo, Begum, Nasim A., Nakajima, Toshiharu, ...

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutations (SHM) and class switch recombination. Overexpression of AID in non-B cells can induce SHM in artificial constructs...

Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes

Wang, Jian, Yoshida, Taku, Nakaki, Fumio, Hiai, Hiroshi, Okazaki, Taku, Honjo, Tasuku

Mice deficient in programmed cell death 1 (PD-1, Pdcd1), an immunoinhibitory receptor belonging to the CD28/cytotoxic T lymphocyte-associated antigen-4 family, spontaneously develop lupus-like...

Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

Kikuchi, Toshiaki, Andarini, Sita, Xin, Hong, Gomi, Kazunori, Tokue, Yutaka, Saijo, Yasuo, ...

Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L....

Negative regulation of activation-induced cytidine deaminase in B cells

Muto, Taro, Okazaki, Il-mi, Yamada, Shuichi, Tanaka, Yoshimasa, Kinoshita, Kazuo, Muramatsu, Masamichi, ...

Both class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes require the activity of activation-induced cytidine deaminase (AID). Expression of AID is restricted to B cells...

Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1α (SDF-1α) and SDF-1β are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage

Shioda, Tatsuo, Kato, Hiroyuki, Ohnishi, Yukano, Tashiro, Kei, Ikegawa, Masaya, Nakayama, Emi E., ...

CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural substrates have not been identified...

The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription

Tani, Shoichi, Kurooka, Hisanori, Aoki, Tomokazu, Hashimoto, Nobuo, Honjo, Tasuku

The evolutionarily-conserved DNA-binding protein RBP-J directly interacts with the RAM domain and the ankyrin (ANK) repeats of the Notch intracellular region (RAMIC), and activates transcription of...

Conservation of the biochemical mechanisms of signal transduction among mammalian Notch family members

Mizutani, Tomohiko, Taniguchi, Yoshihito, Aoki, Tomokazu, Hashimoto, Nobuo, Honjo, Tasuku

Mouse Notch1, which plays an important role in cell fate determination in development, is proteolytically processed within its transmembrane domain by unidentified γ-secretase-like activity that...

A hallmark of active class switch recombination: Transcripts directed by I promoters on looped-out circular DNAs

Kinoshita, Kazuo, Harigai, Motoko, Fagarasan, Sidonia, Muramatsu, Masamichi, Honjo, Tasuku

To specify when and where Ig class switch recombination (CSR) takes place, a good molecular marker closely associated with active CSR is required. CSR is accompanied by deletion of circular DNA from...

Variable deletion and duplication at recombination junction ends: Implication for staggered double-strand cleavage in class-switch recombination

Chen, Xiaochuan, Kinoshita, Kazuo, Honjo, Tasuku

Immunoglobulin class-switch recombination (CSR) gives rise to looped-out circular DNA of a cleaved S segment, which is lost eventually after cell divisions. To understand the molecular mechanism of S...

PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine

Okazaki, Taku, Maeda, Akito, Nishimura, Hiroyuki, Kurosaki, Tomohiro, Honjo, Tasuku

PD-1 is an immunoreceptor that belongs to the immunoglobulin (Ig) superfamily and contains two tyrosine residues in the cytoplasmic region. Studies on PD-1-deficient mice have shown that PD-1 plays...

Functional Replacement of the Intracellular Region of the Notch1 Receptor by Epstein-Barr Virus Nuclear Antigen 2

Sakai, Takashi, Taniguchi, Yoshihito, Tamura, Kumiko, Minoguchi, Shigeru, Fukuhara, Takataro, Strobl, Lothar J., ...

The intracellular region (RAMIC) of the mouse Notch1 receptor interacts with RBP-J/CBF-1, which binds to the DNA sequence CGTGGGAA and suppresses differentiation by transcriptional activation of...

Identification of Notch1 as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

Yanagawa, Shin-ichi, Lee, Jong-Seo, Kakimi, Kazuhiro, Matsuda, Yukihiro, Honjo, Tasuku, Ishimoto, Akinori

In contrast to wild-type mouse mammary tumor virus (MMTV), the MMTV mutants with specific deletions in the U3 region of their long terminal repeats cause T-cell lymphomas. In 30% of T-cell lymphomas...

Intracisternal Type A Particle-Mediated Activation of the Notch4/int3 Gene in a Mouse Mammary Tumor: Generation of Truncated Notch4/int3 mRNAs by Retroviral Splicing Events

Lee, Jong-Seo, Haruna, Tatsuya, Ishimoto, Akinori, Honjo, Tasuku, Yanagawa, Shin-ichi

The int3 oncogene was discovered as a frequent target in mouse mammary tumor virus-induced mammary tumors and encodes the intracellular domain of a Notch4/int3 protein. In one spontaneous mammary...

LIM Protein KyoT2 Negatively Regulates Transcription by Association with the RBP-J DNA-Binding Protein

Taniguchi, Yoshihito, Furukawa, Takahisa, Tun, Tin, Han, Hua, Honjo, Tasuku

The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to...

Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice

Kanatsu-Shinohara, Mito, Ogura, Atsuo, Ikegawa, Masaya, Inoue, Kimiko, Ogonuki, Narumi, Tashiro, Kei, ...

Sertoli cells play a pivotal role in spermatogenesis through their interactions with germ cells. To set up a strategy for treating male infertility caused by Sertoli cell dysfunction, we developed a...

Notch receptor cleavage depends on but is not directly executed by presenilins

Taniguchi, Yoshihito, Karlström, Helena, Lundkvist, Johan, Mizutani, Tomohiko, Otaka, Akira, Vestling, Monica, ...

Notch receptors undergo three distinct proteolytic cleavages during maturation and activation. The third cleavage occurs within the plasma membrane and results in the release and translocation of the...

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade

Iwai, Yoshiko, Ishida, Masayoshi, Tanaka, Yoshimasa, Okazaki, Taku, Honjo, Tasuku, Minato, Nagahiro

PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands (PD-L) and is suggested to play a role in the maintenance...

De novo protein synthesis is required for the activation-induced cytidine deaminase function in class-switch recombination

Doi, Tomomitsu, Kinoshita, Kazuo, Ikegawa, Masaya, Muramatsu, Masamichi, Honjo, Tasuku

Activation-induced cytidine deaminase (AID) is required for class-switch recombination (CSR), somatic hypermutation, and gene conversion of Ig genes. Although AID has sequence similarity to an...

Recombination signal sequence-binding protein Jκ alters mesodermal cell fate decisions by suppressing cardiomyogenesis

Schroeder, Timm, Fraser, Stuart T., Ogawa, Minetaro, Nishikawa, Satomi, Oka, Chio, Bornkamm, Georg W., ...

The transcription factor recombination signal sequence-binding protein Jκ (RBP-J) is a key downstream element in the signaling pathway of all four mammalian Notch receptors that are critically...

RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells

Eto, Tomonori, Kinoshita, Kazuo, Yoshikawa, Kiyotsugu, Muramatsu, Masamichi, Honjo, Tasuku

Antibody diversification by somatic hypermutation, gene conversion, and class switch recombination is completely dependent on activation-induced cytidine deaminase (AID). A recent report showing...

Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1

Ito, Satomi, Nagaoka, Hitoshi, Shinkura, Reiko, Begum, Nasim, Muramatsu, Masamichi, Nakata, Mikiyo, ...

Activation-induced cytidine deaminase (AID) is a molecule central to initiating class switch recombination, somatic hypermutation, and gene conversion of Ig genes. However, its mechanism to initiate...

Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut

Suzuki, Keiichiro, Meek, Bob, Doi, Yasuko, Muramatsu, Masamichi, Chiba, Tsutomu, Honjo, Tasuku, ...

The mechanism to maintain homeostasis of the gut microbiota remains largely unknown despite its critical role in the body defense. In the intestines of mice with deficiency of activation-induced...

Structures of defective P transposable elements prevalent in natural Q and Q-derived M strains of Drosophila melanogaster

Sakoyama, Yasuhiko, Todo, Takeshi, Ishiwa-Chigusa, Sadao, Honjo, Tasuku, Kondo, Sohei

Several DNA sequences with homology to the complete 2.9-kilobase (kb) P element from a P strain in the United States were isolated and characterized from two Drosophila melanogaster strains collected...

The Organization and Diversity of Immunoglobulin Genes*

Leder, Philip, Honjo, Tasuku, Packman, Seymour, Swan, David, Nau, Marion, Norman, Barbara

We have used purified mouse immunoglobulin light chain mRNA and synthetic DNA which is complementary to it to assess the reiteration frequency of gene sequences corresponding to the κ constant...

De novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination

Begum, Nasim A., Kinoshita, Kazuo, Muramatsu, Masamichi, Nagaoka, Hitoshi, Shinkura, Reiko, Honjo, Tasuku

Activation-induced cytidine deaminase is required for the DNA cleavage step of Ig class switch recombination (CSR). However, its molecular mechanism is controversial. RNA-editing hypothesis...

Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants

Krebs, Luke T., Shutter, John R., Tanigaki, Kenji, Honjo, Tasuku, Stark, Kevin L., Gridley, Thomas

The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand...

DNA cleavage in immunoglobulin somatic hypermutation depends on de novo protein synthesis but not on uracil DNA glycosylase

Nagaoka, Hitoshi, Ito, Satomi, Muramatsu, Masamichi, Nakata, Mikiyo, Honjo, Tasuku

Activation-induced cytidine deaminase (AID) is required for the DNA cleavage step of Ig somatic hypermutation (SHM). However, its molecular mechanism is controversial. The RNA editing hypothesis...

Two distinctive pathways for recruitment of naïve and primed IgM+ B cells to the gut lamina propria

Suzuki, Keiichiro, Meek, Bob, Doi, Yasuko, Honjo, Tasuku, Fagarasan, Sidonia

Intestinal IgA+ B cells are generated from IgM+ B cells by in situ class switching in two separate gut microenvironments: organized follicular structures and lamina propria (LP). However, the origin...

A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression

Kotani, Ai, Okazaki, Il-mi, Muramatsu, Masamichi, Kinoshita, Kazuo, Begum, Nasim A., Nakajima, Toshiharu, ...

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutations (SHM) and class switch recombination. Overexpression of AID in non-B cells can induce SHM in artificial constructs...

Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes

Wang, Jian, Yoshida, Taku, Nakaki, Fumio, Hiai, Hiroshi, Okazaki, Taku, Honjo, Tasuku

Mice deficient in programmed cell death 1 (PD-1, Pdcd1), an immunoinhibitory receptor belonging to the CD28/cytotoxic T lymphocyte-associated antigen-4 family, spontaneously develop lupus-like...

Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

Kikuchi, Toshiaki, Andarini, Sita, Xin, Hong, Gomi, Kazunori, Tokue, Yutaka, Saijo, Yasuo, ...

Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L....

Negative regulation of activation-induced cytidine deaminase in B cells

Muto, Taro, Okazaki, Il-mi, Yamada, Shuichi, Tanaka, Yoshimasa, Kinoshita, Kazuo, Muramatsu, Masamichi, ...

Both class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes require the activity of activation-induced cytidine deaminase (AID). Expression of AID is restricted to B cells...

Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice

Kotani, Ai, Kakazu, Naoki, Tsuruyama, Tatsuaki, Okazaki, Il-mi, Muramatsu, Masamichi, Kinoshita, Kazuo, ...

Activation-induced cytidine deaminase (AID), which is essential to both class switch recombination and somatic hypermutation of the Ig gene, is expressed in many types of human B cell...

Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling

Tsuji, Masayuki, Shinkura, Reiko, Kuroda, Kazuki, Yabe, Daisuke, Honjo, Tasuku

Notch/RBP-J signaling is required for generation of early T progenitors (ETP) and promotion of double-negative (DN) 4 cells from DN3 cells in thymocyte differentiation. However, whether Notch affects...

Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer

Hamanishi, Junzo, Mandai, Masaki, Iwasaki, Masashi, Okazaki, Taku, Tanaka, Yoshimasa, Yamaguchi, Ken, ...

The ligands for programmed cell death 1 (PD-1), an immunoinhibitory receptor belonging to CD28/cytotoxic T lymphocyte antigen 4 family, are PD-1 ligand 1 and 2 (PD-Ls). Recent reports suggest that...

Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b−/−Pdcd1−/− mice

Okazaki, Taku, Otaka, Yumi, Wang, Jian, Hiai, Hiroshi, Takai, Toshiyuki, Ravetch, Jeffrey V., ...

Because most autoimmune diseases are polygenic, analysis of the synergistic involvement of various immune regulators is essential for a complete understanding of the molecular pathology of these...

Unmutated Immunoglobulin M Can Protect Mice from Death by Influenza Virus Infection

Harada, Yuichi, Muramatsu, Masamichi, Shibata, Toshikatsu, Honjo, Tasuku, Kuroda, Kazumichi

To elucidate the role of class switch recombination (CSR) and somatic hypermutation (SHM) in virus infection, we have investigated the influence of the primary and secondary infections of influenza...

Constitutive Expression of AID Leads to Tumorigenesis

Okazaki, Il-mi, Hiai, Hiroshi, Kakazu, Naoki, Yamada, Shuichi, Muramatsu, Masamichi, Kinoshita, Kazuo, ...

Genome stability is regulated by the balance between efficiencies of the repair machinery and genetic alterations such as mutations and chromosomal rearrangements. It has been postulated that...

Molecular Modeling and Functional Mapping of B7-H1 and B7-DC Uncouple Costimulatory Function from PD-1 Interaction

Wang, Shengdian, Bajorath, Jürgen, Flies, Dallas B., Dong, Haidong, Honjo, Tasuku, Chen, Lieping

B7-H1 and B7-DC are ligands for PD-1, a receptor implicated in negative regulation of T and B cell functions. These ligands, however, also costimulate T cell responses. It remains elusive whether or...

Activation and Differentiation of Autoreactive B-1 Cells by Interleukin 10 Induce Autoimmune Hemolytic Anemia in Fas-deficient Antierythrocyte Immunoglobulin Transgenic Mice

Watanabe, Norihiko, Ikuta, Koichi, Nisitani, Sazuku, Chiba, Tsutomu, Honjo, Tasuku

The Fas (CD95) gene is among critical genetic factors in some autoimmune diseases, which are characterized by autoantibody (autoAb) productions. In mice, mutations in the Fas gene cause...

PD-1 Inhibits Antiviral Immunity at the Effector Phase in the Liver

Iwai, Yoshiko, Terawaki, Seigo, Ikegawa, Masaya, Okazaki, Taku, Honjo, Tasuku

Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot...

Migration and Differentiation of Autoreactive B-1 Cells Induced by Activated γ/δ T Cells in Antierythrocyte Immunoglobulin Transgenic Mice

Watanabe, Norihiko, Ikuta, Koichi, Fagarasan, Sidonia, Yazumi, Shujiro, Chiba, Tsutomu, Honjo, Tasuku

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 cells are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they...

Markedly Different Pathogenicity of Four Immunoglobulin G Isotype-Switch Variants of an Antierythrocyte Autoantibody Is Based on Their Capacity to Interact in Vivo with the Low-Affinity Fcγ Receptor III

Fossati-Jimack, Liliane, Ioan-Facsinay, Andreea, Reininger, Luc, Chicheportiche, Yves, Watanabe, Norihiko, Saito, Takashi, ...

Using three different Fcγ receptor (FcγR)-deficient mouse strains, we examined the induction of autoimmune hemolytic anemia by each of the four immunoglobulin (Ig)G isotype-switch variants of a 4C8...

Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation

Freeman, Gordon J., Long, Andrew J., Iwai, Yoshiko, Bourque, Karen, Chernova, Tatyana, Nishimura, Hiroyuki, ...

PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune...

Histone Acetylation Determines the Developmentally Regulated Accessibility for T Cell Receptor γ Gene Recombination

Agata, Yasutoshi, Katakai, Tomoya, Ye, Sang-Kyu, Sugai, Manabu, Gonda, Hiroyuki, Honjo, Tasuku, ...

Variable/diversity/joining (V[D]J) recombination of the T cell receptor (TCR) and immunoglobulin (Ig) genes is regulated by chromatin accessibility of the target locus to the recombinase in a...

Quantitative Regulation of Class Switch Recombination by Switch Region Transcription

Lee, Chung-Gi, Kinoshita, Kazuo, Arudchandran, Arulvathani, Cerritelli, Susana M., Crouch, Robert J., Honjo, Tasuku

The isotype specificity of immunoglobulin (Ig) class switching is regulated by a cytokine which induces transcription of a specific switch (S) region, giving rise to so-called germline transcripts....

Activation-induced Deaminase (AID)-directed Hypermutation in the Immunoglobulin Sμ Region: Implication of AID Involvement in a Common Step of Class Switch Recombination and Somatic Hypermutation

Nagaoka, Hitoshi, Muramatsu, Masamichi, Yamamura, Namiko, Kinoshita, Kazuo, Honjo, Tasuku

Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions...

DNA Double-Strand Breaks: Prior to but not Sufficient in Targeting Hypermutation

Bross, Linda, Muramatsu, Masamichi, Kinoshita, Kazuo, Honjo, Tasuku, Jacobs, Heinz

The activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin (Ig) genes, both of which are associated with DNA...

Expression Levels of B Cell Surface Immunoglobulin Regulate Efficiency of Allelic Exclusion and Size of Autoreactive B-1 Cell Compartment

Watanabe, Norihiko, Nisitani, Sazuku, Ikuta, Koichi, Suzuki, Misao, Chiba, Tsutomu, Honjo, Tasuku

Surface-expressed immunoglobulin (Ig) has been shown to have a critical role in allelic exclusion of Ig heavy (H) and light (L) chains. Although various degrees of suppression of endogenous Ig...

High Pathogenic Potential of Low-Affinity Autoantibodies in Experimental Autoimmune Hemolytic Anemia

Fossati-Jimack, Liliane, Reininger, Luc, Chicheportiche, Yves, Clynes, Raphael, Ravetch, Jeffrey V., Honjo, Tasuku, ...

To assess the potency of low-affinity anti–red blood cell (RBC) autoantibodies in the induction of anemia, we generated an immunoglobulin (Ig)G2a class-switch variant of a 4C8 IgM anti–mouse RBC...

Lineage-Restricted Function of Nuclear Factor κB–Inducing Kinase (Nik) in Transducing Signals via Cd40

Garceau, Norman, Kosaka, Yoko, Masters, Sally, Hambor, John, Shinkura, Reiko, Honjo, Tasuku, ...

CD40 signaling in B cells and dendritic cells (DCs) is critical for the development of humoral and cell-mediated immunity, respectively. Nuclear factor κB (NF-κB)–inducing kinase (NIK) has been...

Facilitation of β Selection and Modification of Positive Selection in the Thymus of Pd-1–Deficient Mice

Nishimura, Hiroyuki, Honjo, Tasuku, Minato, Nagahiro

PD-1 is an immunoglobulin superfamily member bearing an immunoreceptor tyrosine-based inhibitory motif, and disruption of the PD-1 gene results in the development of lupus-like autoimmune diseases....

Effects of Breeding Environments on Generation and Activation of Autoreactive B-1 Cells in Anti-red Blood Cell Autoantibody Transgenic Mice

Murakami, Masao, Nakajima, Kazuo, Yamazaki, Ken-ichi, Muraguchi, Takehiko, Serikawa, Tadao, Honjo, Tasuku

In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut. About one-half of the auto Ab Tg mice suffer...

The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus

Matsuda, Fumihiko, Ishii, Kazuo, Bourvagnet, Patrice, Kuma, Kei-ichi, Hayashida, Hidenori, Miyata, Takashi, ...

The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (VH) region locus was determined and 43 novel VH segments were identified. The region contains 123...

Alymphoplasia (aly)-Type Nuclear Factor κB–Inducing Kinase (Nik) Causes Defects in Secondary Lymphoid Tissue Chemokine Receptor Signaling and Homing of Peritoneal Cells to the Gut-Associated Lymphatic Tissue System

Fagarasan, Sidonia, Shinkura, Reiko, Kamata, Tadashi, Nogaki, Fumiaki, Ikuta, Koichi, Tashiro, Kei, ...

Alymphoplasia (aly) mice, which carry a point mutation in the nuclear factor κB–inducing kinase (NIK) gene, are characterized by the systemic absence of lymph nodes and Peyer's patches,...

AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements

Kovalchuk, Alexander L., DuBois, Wendy, Mushinski, Elizabeth, McNeil, Nicole E., Hirt, Carsten, Qi, Chen-Feng, ...

Activation-induced cytidine deaminase (AID) is required for immunoglobulin (Ig) class switch recombination and somatic hypermutation, and has also been implicated in translocations between Ig switch...

The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome▿

Green, Kathy A., Okazaki, Taku, Honjo, Tasuku, Cook, W. James, Green, William R.

Pathology due to the immune system's response to viral infections often represents a delicate balance between inhibition of viral pathogenesis and regulation of protective immunity. In susceptible...

The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors

Lin, David Yin-wei, Tanaka, Yoshimasa, Iwasaki, Masashi, Gittis, Apostolos G., Su, Hua-Poo, Mikami, Bunzo, ...

Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors and plays an important role in the...

PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice

Yoshida, Taku, Jiang, Fang, Honjo, Tasuku, Okazaki, Taku

Although many autoimmune diseases are associated with particular HLA/H-2 haplotypes, the mechanisms through which specific HLA/H-2 haplotypes afford autoimmune susceptibility remain enigmatic. Here,...

Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2

Riccio, Orbicia, Van Gijn, Marielle E, Bezdek, April C, Pellegrinet, Luca, Van Es, Johan H, Zimber-Strobl, Ursula, ...

The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice....

Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants

Shivarov, Velizar, Shinkura, Reiko, Honjo, Tasuku

Activation-induced cytidine deaminase (AID) is essential for the DNA cleavage that initiates both somatic hypermutation (SHM) and class switch recombination (CSR) of the Ig gene. Two alternative...

Carboxy-terminal domain of AID required for its mRNA complex formation in vivo

Nonaka, Taichiro, Doi, Tomomitsu, Toyoshima, Takae, Muramatsu, Masamichi, Honjo, Tasuku, Kinoshita, Kazuo

Activation-induced cytidine deaminase (AID) is essential for the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. Originally, AID was postulated to be an RNA-editing...

The C-terminal region of activation-induced cytidine deaminase is responsible for a recombination function other than DNA cleavage in class switch recombination

Doi, Tomomitsu, Kato, Lucia, Ito, Satomi, Shinkura, Reiko, Wei, Min, Nagaoka, Hitoshi, ...

Activation-induced cytidine deaminase (AID) is an essential factor for the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. CSR and SHM are initiated by AID-induced DNA...

Further evidence for involvement of a noncanonical function of uracil DNA glycosylase in class switch recombination

Begum, Nasim A., Stanlie, Andre, Doi, Tomomitsu, Sasaki, Yoko, Jin, Hai Wei, Kim, Yong Sung, ...

Activation-induced cytidine deaminase (AID) introduces DNA cleavage in the Ig gene locus to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells. The DNA deamination...

Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway

Haspot, Fabienne, Fehr, Thomas, Gibbons, Carrie, Zhao, Guiling, Hogan, Timothy, Honjo, Tasuku, ...

Although interaction between programmed death-1 (PD-1) and the ligand PD-L1 has been shown to mediate CD8 cell exhaustion in the setting of chronic infection or the absence of CD4 help, a role for...