Derudder, Emmanuel, Cadera, Emily J., Val, J. Christoph, Wang, Jing, Fox, Casey J., Zha, Shan, ...
By genetically ablating I kappa B kinase (IKK)-mediated activation of the transcription factor NF-kappa B in the B cell lineage and by analyzing a mouse mutant in which immunoglobulin...
Hair loss and defective T- and B-cell function in mice lacking ORAI1 (2008)
Gwack, Yousang, Srikanth, Sonal, Oh-Hora, Masatsugu, Hogan, Patrick G., Lamperti, Edward D., Yamashita, Megumi, ...
ORAI1 is a pore subunit of the store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel. To examine the physiological consequences of ORAI1 deficiency, we generated mice with targeted disruption...
Yin Yang 1 is a critical regulator of B-cell development (2007)
Liu, Huifei, Schmidt-Supprian, Marc, Shi, Yujiang, Hobeika, Elias, Barteneva, Natasha, Jumaa, Hassan, ...
The role of the transcription factor Yin Yang 1 (YY1) in development is largely unknown. Here we show that specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the...
Nenci, Arianna, Huth, Marion, Funteh, Alfred, Schmidt-Supprian, Marc, Bloch, Wilhelm, Metzger, Daniel, ...
NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase, is essential for NF-κB activation. Mutations disrupting the X-linked NEMO gene cause incontinentia pigmenti (IP), a...
Nenci, Arianna, Huth, Marion, Funteh, Alfred, Schmidt-Supprian, Marc, Bloch, Wilhelm, Metzger, Daniel, ...
NF-κB Essential Modulator (NEMO), the regulatory subunit of the IκB kinase, is essential for NF-κB activation. Mutations disrupting the X-linked NEMO gene cause incontinentia pigmenti (IP), a...
MicroRNA profiling of the murine hematopoietic system (2005)
Monticelli, Silvia, Ansel, K Mark, Xiao, Changchun, Socci, Nicholas D, Krichevsky, Anna M, Thai, To-Ha, ...
Abstract Background MicroRNAs (miRNAs) are a class of recently discovered noncoding RNA genes that post-transcriptionally regulate gene expression. It is becoming clear that miRNAs play an important...
Assmus, Ulrike, Wüstefeld, Torsten, Meyer Zu Vilsendorf, Andreas, Schmidt-Supprian, Mark, ...
The inhibitor of NF-kappaB (I-kappaB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-kappaB essential modulator (NEMO), and is involved in the activation of NF-kappaB by various...
Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells (2005)
Lina E. Tze, Brian R. Schram, Kong-Peng Lam, Kristin A. Hogquist, Keli L. Hippen, Jiabin Liu, ...
Gene rearrangement is a hallmark of B cell maturation. By interrupting basal cell signaling through the rearranged IgM receptor, immature B cells "back-differentiate" to an earlier stage in their...
Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells (2005)
Lina E. Tze, Brian R. Schram, Kong-Peng Lam, Kristin A. Hogquist, Keli L. Hippen, Jiabin Liu, ...
In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B...
Kanellopoulou, Chryssa, Muljo, Stefan A., Kung, Andrew L., Ganesan, Shridar, Drapkin, Ronny, Jenuwein, Thomas, ...
Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21–25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or...
Skulina, Christian, Schmidt, Stephan, Dornmair, Klaus, Babbe, Holger, Roers, Axel, Rajewsky, Klaus, ...
Unidirectional Cre-mediated genetic inversion in mice using the mutant loxP pair lox66/lox71 (2003)
Oberdoerffer, Philipp, Otipoby, Kevin L., Maruyama, Mitsuo, Rajewsky, Klaus
The Cre/loxP recombination system is a commonly used tool to alter the mouse genome in a conditional manner by deletion or inversion of loxP‐flanked DNA segments. While Cre‐mediated...
Rapid generation of inducible mouse mutants (2003)
Seibler, Jost, Zevnik, Branko, Küter-Luks, Birgit, Andreas, Susanne, Kern, Heidrun, Hennek, Thomas, ...
We have generated an optimized inducible recombination system for conditional gene targeting based on a Cre recombinase–steroid receptor fusion. This configuration allows efficient...
Stringent doxycycline dependent control of CRE recombinase in vivo (2002)
Schönig, Kai, Schwenk, Frieder, Rajewsky, Klaus, Bujard, Hermann
The strategy of modulating gene activities in vivo via CRE/loxP recombination would greatly profit from subjecting the recombination event to an independent and stringent temporal control. Here, we...
Wunderlich, Frank T., Wildner, Hendrik, Rajewsky, Klaus, Edenhofer, Frank
We have developed a novel inducible Cre mutant with enhanced recombinase activity to mediate genetic switching events. The protein, designated Cre*PR, is composed of a new Cre mutant at the...
Antibodies generated from human immunoglobulin miniloci in transgenic mice (1994)
Wagner, Simon D., Williams, Gareth T., Larson, Tammy, Neuberger, Michael S., Kitamura, Daisuke, Rajewsky, Klaus, ...
One approach to the production of human monoclonal antibodies focusses on the creation of transgenic mice bearing human immunoglobulin gene miniloci. Whilst such loci undergo lymphold-speclfic gene...
Simon, Thomas, Rajewsky, Klaus
We have studied the effects of a four residue insertion into the FR3 loop of the heavy chain variable region from the anti-NP antibody Bl-8. The insertion mutant is obtained as secreted antibody...
Cell autonomous expression of IgD is not essential for the maturation of conventional B cells (1991)
To analyse the function of IgD in vivo, we generated a ‘loss of function’ mouse model utilizing gene targeting technology. By homologous recombination in a (C57BL/6 × CBA)F1 mouse embryonic...
Persistence of memory B cells in mice deprived of T cell help (1990)
Vieira, Paulo, Rajewsky, Klaus
The influence of T cell help on the Induction, maintenance, and recall of B cell memory to a T cell-dependent antigen was studied in mice. The antigen was a hapten coupled to a protein carrier, and...
Violation of allelic exclusion of the T cell receptor {beta} genes in a helper T cell clone (1989)
Schittek, Birgit, Unkelbach, Elvira, Rajewsky, Klaus, Radbruch, A
The 4-hydroxy-3-nltrophenylacetyl coupled to chicken gamma globulin specific and I-Ab restricted helper T cell clone IH4 carries a Vβ8 1–Dβ2.1–Jβ2.3-rearrangement on one and a...
Förster, Irmgard, Vieira, Paulo, Rajewsky, Klaus, Okumura, K.
Using a method which allows simultaneous flow cytometric detection of cell surface markers and 5-bromo-2'-deoxyuridine (BrdU) incorporation, the distribution and proliferative behavior of B lineage...
Vergleich der Primärstrukturen multipler und differenter Lactatdehydrogenasen. (1962)
Frankfurt, Med. F., Diss. v. 2. Okt. 1962.
Esposito, Gloria, Texido, Gemma, Betz, Ulrich A. K., Gu, Hua, Müller, Werner, Klein, Ulf, ...
The ubiquitously expressed, error-prone DNA polymerase β (polβ) plays a role in base excision repair, and the involvement of this molecule in the nonhomologous end joining (NHEJ) process of DNA...
Braun, Uschi, Rajewsky, Klaus, Pelanda, Roberta
Ig knock-in mice have been used to study the relative contribution of receptor selection versus clonal selection in the control of autoreactive B cells. The anti-MHC class I 3-83Ig knock-in (3-83Igi)...
Isolation of viable Hodgkin and Reed-Sternberg cells from Hodgkin disease tissues
Irsch, Johannes, Nitsch, Silke, Hansmann, Martin-Leo, Rajewsky, Klaus, Tesch, Hans, Diehl, Volker, ...
Hodgkin disease (HD) is characterized by a small number of malignant Hodgkin and Reed-Sternberg (H/RS) cells among a major population of nonmalignant cells. The analysis of H/RS cells has been...
Pasqualucci, Laura, Migliazza, Anna, Fracchiolla, Nicola, William, Christopher, Neri, Antonino, Baldini, Luca, ...
The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown, but it is commonly believed that this mechanism is restricted to the Ig loci. B cell...
Abnormal development of secondary lymphoid tissues in lymphotoxin β-deficient mice
Alimzhanov, Marat B., Kuprash, Dmitry V., Kosco-Vilbois, Marie H., Luz, Arne, Turetskaya, Regina L., Tarakhovsky, Alexander, ...
The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) α and LTβ form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LTα homotrimers...
Braeuninger, Andreas, Küppers, Ralf, Strickler, John G., Wacker, Hans-Heinrich, Rajewsky, Klaus, Hansmann, Martin-Leo
Among the four subtypes of Hodgkin disease (HD), lymphocyte-predominant (LP) HD is now generally considered as a separate entity. The B cell nature of the typical Hodgkin and Reed–Sternberg (HRS)...
Lam, Kong-Peng, Rajewsky, Klaus
Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated...
How αβ T cells deal with induced TCRα ablation
Polic, Bojan, Kunkel, Desiree, Scheffold, Alexander, Rajewsky, Klaus
On deletion of the gene encoding the constant region of the T cell antigen receptor (TCR)α chain in mature T cells by induced Cre-mediated recombination, the cells lose most of their TCR from the...
Wunderlich, Frank T., Wildner, Hendrik, Rajewsky, Klaus, Edenhofer, Frank
We have developed a novel inducible Cre mutant with enhanced recombinase activity to mediate genetic switching events. The protein, designated Cre*PR, is composed of a new Cre mutant at the...
The B-Cell-Specific src-Family Kinase Blk Is Dispensable for B-Cell Development and Activation
Texido, Gemma, Su, I-hsin, Mecklenbräuker, Ingrid, Saijo, Kaoru, Malek, Sami N., Desiderio, Stephen, ...
The B-cell lymphocyte kinase (Blk) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells of mice. The early onset of Blk expression during B-cell development in the bone...
Peitz, Michael, Pfannkuche, Kurt, Rajewsky, Klaus, Edenhofer, Frank
Conditional mutagenesis is a powerful tool to analyze gene functions in mammalian cells. The site-specific recombinase Cre can be used to recombine loxP-modified alleles under temporal and spatial...
Stringent doxycycline dependent control of CRE recombinase in vivo
Schönig, Kai, Schwenk, Frieder, Rajewsky, Klaus, Bujard, Hermann
The strategy of modulating gene activities in vivo via CRE/loxP recombination would greatly profit from subjecting the recombination event to an independent and stringent temporal control. Here, we...
Kuprash, Dmitry V., Alimzhanov, Marat B., Tumanov, Alexei V., Grivennikov, Sergei I., Shakhov, Alexander N., Drutskaya, Ludmila N., ...
Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation,...
Rapid generation of inducible mouse mutants
Seibler, Jost, Zevnik, Branko, Küter-Luks, Birgit, Andreas, Susanne, Kern, Heidrun, Hennek, Thomas, ...
We have generated an optimized inducible recombination system for conditional gene targeting based on a Cre recombinase–steroid receptor fusion. This configuration allows efficient Cre-mediated...
Kurth, Julia, Hansmann, Martin-Leo, Rajewsky, Klaus, Küppers, Ralf
To assess the impact of the germinal center (GC) reaction on viral spread in Epstein–Barr virus (EBV) infection, we isolated EBV+ GC B cells from the tonsils of two infectious mononucleosis...
Kanters, Edwin, Pasparakis, Manolis, Gijbels, Marion J.J., Vergouwe, Monique N., Partouns-Hendriks, Iris, Fijneman, Remond J.A., ...
Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-κB is a key regulator of inflammation, immune responses, cell survival, and cell...
Unidirectional Cre-mediated genetic inversion in mice using the mutant loxP pair lox66/lox71
Oberdoerffer, Philipp, Otipoby, Kevin L., Maruyama, Mitsuo, Rajewsky, Klaus
The Cre/loxP recombination system is a commonly used tool to alter the mouse genome in a conditional manner by deletion or inversion of loxP-flanked DNA segments. While Cre-mediated deletion is...
Conditional disruption of IκB kinase 2 fails to prevent obesity-induced insulin resistance
Röhl, Mathias, Pasparakis, Manolis, Baudler, Stephanie, Baumgartl, Julia, Gautam, Dinesh, Huth, Marion, ...
The inhibitor of NF-κB (IκB) kinases (IKK1[α] and IKK2[β]), the catalytic subunits of the IKK complex, phosphorylate IκB proteins on serine residues, targeting them for degradation and thus...
Skulina, Christian, Schmidt, Stephan, Dornmair, Klaus, Babbe, Holger, Roers, Axel, Rajewsky, Klaus, ...
We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to...
Schmidt-Supprian, Marc, Tian, Jane, Grant, Ethan P., Pasparakis, Manolis, Maehr, René, Ovaa, Huib, ...
Natural killer-like (NK) T, regulatory T (TR), and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of TR cells and, to a...
Kanellopoulou, Chryssa, Muljo, Stefan A., Kung, Andrew L., Ganesan, Shridar, Drapkin, Ronny, Jenuwein, Thomas, ...
Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21–25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or...
Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells
Tze, Lina E, Schram, Brian R, Lam, Kong-Peng, Hogquist, Kristin A, Hippen, Keli L, Liu, Jiabin, ...
In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B...
Luedde, Tom, Assmus, Ulrike, Wüstefeld, Torsten, Meyer Zu Vilsendorf, Andreas, Roskams, Tania, Schmidt-Supprian, Mark, ...
The inhibitor of NF-κB (I-κB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-κB essential modulator (NEMO), and is involved in the activation of NF-κB by various stimuli. IKK2 or...
Oberdoerffer, Philipp, Kanellopoulou, Chryssa, Heissmeyer, Vigo, Paeper, Corinna, Borowski, Christine, Aifantis, Iannis, ...
RNA interference (RNAi) is a naturally occurring posttranscriptional gene-silencing mechanism that has been adapted as a genetic tool for loss-of-function studies of a variety of organisms. It is...
Direct in vivo VH to JH rearrangement violating the 12/23 rule
Koralov, Sergei B., Novobrantseva, Tatiana I., Hochedlinger, Konrad, Jaenisch, Rudolf, Rajewsky, Klaus
V(D)J recombination at the immunoglobulin heavy chain (IgH) locus follows the 12/23 rule to ensure the correct assembly of the variable region gene segments. Here, we report characterization of an in...
MicroRNA profiling of the murine hematopoietic system
Monticelli, Silvia, Ansel, K Mark, Xiao, Changchun, Socci, Nicholas D, Krichevsky, Anna M, Thai, To-Ha, ...
The first report of systematic miRNA profiling in cells of the hematopoietic system suggests that, in addition to regulating commitment to particular cellular lineages, miRNAs might have a general...
Schwering, Ines, Bräuninger, Andreas, Distler, Verena, Jesdinsky, Julia, Diehl, Volker, Hansmann, Martin-Leo, ...
The malignant cells of classical Hodgkin’s lymphoma (cHL), Hodgkin and Reed-Sternberg (HRS) cells, appear to be derived from germinal center (GC) B cells in most cases of the disease. Apart from...
Casola, Stefano, Cattoretti, Giorgio, Uyttersprot, Nathalie, Koralov, Sergei B., Segal, Jane, Hao, Zhenyue, ...
Germinal centers (GCs) represent the main sites for the generation of high-affinity, class-switched antibodies during T cell-dependent antibody responses. To study gene function specifically in GC B...
Esposito, Gloria, Texido, Gemma, Betz, Ulrich A. K., Gu, Hua, Müller, Werner, Klein, Ulf, ...
The ubiquitously expressed, error-prone DNA polymerase β (polβ) plays a role in base excision repair, and the involvement of this molecule in the nonhomologous end joining (NHEJ) process of DNA...
Braun, Uschi, Rajewsky, Klaus, Pelanda, Roberta
Ig knock-in mice have been used to study the relative contribution of receptor selection versus clonal selection in the control of autoreactive B cells. The anti-MHC class I 3-83Ig knock-in (3-83Igi)...
Isolation of viable Hodgkin and Reed-Sternberg cells from Hodgkin disease tissues
Irsch, Johannes, Nitsch, Silke, Hansmann, Martin-Leo, Rajewsky, Klaus, Tesch, Hans, Diehl, Volker, ...
Hodgkin disease (HD) is characterized by a small number of malignant Hodgkin and Reed-Sternberg (H/RS) cells among a major population of nonmalignant cells. The analysis of H/RS cells has been...
Pasqualucci, Laura, Migliazza, Anna, Fracchiolla, Nicola, William, Christopher, Neri, Antonino, Baldini, Luca, ...
The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown, but it is commonly believed that this mechanism is restricted to the Ig loci. B cell...
Abnormal development of secondary lymphoid tissues in lymphotoxin β-deficient mice
Alimzhanov, Marat B., Kuprash, Dmitry V., Kosco-Vilbois, Marie H., Luz, Arne, Turetskaya, Regina L., Tarakhovsky, Alexander, ...
The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) α and LTβ form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LTα homotrimers...
Braeuninger, Andreas, Küppers, Ralf, Strickler, John G., Wacker, Hans-Heinrich, Rajewsky, Klaus, Hansmann, Martin-Leo
Among the four subtypes of Hodgkin disease (HD), lymphocyte-predominant (LP) HD is now generally considered as a separate entity. The B cell nature of the typical Hodgkin and Reed–Sternberg (HRS)...
Lam, Kong-Peng, Rajewsky, Klaus
Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated...
How αβ T cells deal with induced TCRα ablation
Polic, Bojan, Kunkel, Desiree, Scheffold, Alexander, Rajewsky, Klaus
On deletion of the gene encoding the constant region of the T cell antigen receptor (TCR)α chain in mature T cells by induced Cre-mediated recombination, the cells lose most of their TCR from the...
Wunderlich, Frank T., Wildner, Hendrik, Rajewsky, Klaus, Edenhofer, Frank
We have developed a novel inducible Cre mutant with enhanced recombinase activity to mediate genetic switching events. The protein, designated Cre*PR, is composed of a new Cre mutant at the...
The B-Cell-Specific src-Family Kinase Blk Is Dispensable for B-Cell Development and Activation
Texido, Gemma, Su, I-hsin, Mecklenbräuker, Ingrid, Saijo, Kaoru, Malek, Sami N., Desiderio, Stephen, ...
The B-cell lymphocyte kinase (Blk) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells of mice. The early onset of Blk expression during B-cell development in the bone...
Peitz, Michael, Pfannkuche, Kurt, Rajewsky, Klaus, Edenhofer, Frank
Conditional mutagenesis is a powerful tool to analyze gene functions in mammalian cells. The site-specific recombinase Cre can be used to recombine loxP-modified alleles under temporal and spatial...
Stringent doxycycline dependent control of CRE recombinase in vivo
Schönig, Kai, Schwenk, Frieder, Rajewsky, Klaus, Bujard, Hermann
The strategy of modulating gene activities in vivo via CRE/loxP recombination would greatly profit from subjecting the recombination event to an independent and stringent temporal control. Here, we...
Kuprash, Dmitry V., Alimzhanov, Marat B., Tumanov, Alexei V., Grivennikov, Sergei I., Shakhov, Alexander N., Drutskaya, Ludmila N., ...
Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation,...
Rapid generation of inducible mouse mutants
Seibler, Jost, Zevnik, Branko, Küter-Luks, Birgit, Andreas, Susanne, Kern, Heidrun, Hennek, Thomas, ...
We have generated an optimized inducible recombination system for conditional gene targeting based on a Cre recombinase–steroid receptor fusion. This configuration allows efficient Cre-mediated...
Kurth, Julia, Hansmann, Martin-Leo, Rajewsky, Klaus, Küppers, Ralf
To assess the impact of the germinal center (GC) reaction on viral spread in Epstein–Barr virus (EBV) infection, we isolated EBV+ GC B cells from the tonsils of two infectious mononucleosis...
Kanters, Edwin, Pasparakis, Manolis, Gijbels, Marion J.J., Vergouwe, Monique N., Partouns-Hendriks, Iris, Fijneman, Remond J.A., ...
Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-κB is a key regulator of inflammation, immune responses, cell survival, and cell...
Unidirectional Cre-mediated genetic inversion in mice using the mutant loxP pair lox66/lox71
Oberdoerffer, Philipp, Otipoby, Kevin L., Maruyama, Mitsuo, Rajewsky, Klaus
The Cre/loxP recombination system is a commonly used tool to alter the mouse genome in a conditional manner by deletion or inversion of loxP-flanked DNA segments. While Cre-mediated deletion is...
Conditional disruption of IκB kinase 2 fails to prevent obesity-induced insulin resistance
Röhl, Mathias, Pasparakis, Manolis, Baudler, Stephanie, Baumgartl, Julia, Gautam, Dinesh, Huth, Marion, ...
The inhibitor of NF-κB (IκB) kinases (IKK1[α] and IKK2[β]), the catalytic subunits of the IKK complex, phosphorylate IκB proteins on serine residues, targeting them for degradation and thus...
Skulina, Christian, Schmidt, Stephan, Dornmair, Klaus, Babbe, Holger, Roers, Axel, Rajewsky, Klaus, ...
We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to...
Schmidt-Supprian, Marc, Tian, Jane, Grant, Ethan P., Pasparakis, Manolis, Maehr, René, Ovaa, Huib, ...
Natural killer-like (NK) T, regulatory T (TR), and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of TR cells and, to a...
Kanellopoulou, Chryssa, Muljo, Stefan A., Kung, Andrew L., Ganesan, Shridar, Drapkin, Ronny, Jenuwein, Thomas, ...
Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21–25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or...
Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells
Tze, Lina E, Schram, Brian R, Lam, Kong-Peng, Hogquist, Kristin A, Hippen, Keli L, Liu, Jiabin, ...
In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B...
Luedde, Tom, Assmus, Ulrike, Wüstefeld, Torsten, Meyer Zu Vilsendorf, Andreas, Roskams, Tania, Schmidt-Supprian, Mark, ...
The inhibitor of NF-κB (I-κB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-κB essential modulator (NEMO), and is involved in the activation of NF-κB by various stimuli. IKK2 or...
Oberdoerffer, Philipp, Kanellopoulou, Chryssa, Heissmeyer, Vigo, Paeper, Corinna, Borowski, Christine, Aifantis, Iannis, ...
RNA interference (RNAi) is a naturally occurring posttranscriptional gene-silencing mechanism that has been adapted as a genetic tool for loss-of-function studies of a variety of organisms. It is...
MicroRNA profiling of the murine hematopoietic system
Monticelli, Silvia, Ansel, K Mark, Xiao, Changchun, Socci, Nicholas D, Krichevsky, Anna M, Thai, To-Ha, ...
The first report of systematic miRNA profiling in cells of the hematopoietic system suggests that, in addition to regulating commitment to particular cellular lineages, miRNAs might have a general...
Schwering, Ines, Bräuninger, Andreas, Distler, Verena, Jesdinsky, Julia, Diehl, Volker, Hansmann, Martin-Leo, ...
The malignant cells of classical Hodgkin’s lymphoma (cHL), Hodgkin and Reed-Sternberg (HRS) cells, appear to be derived from germinal center (GC) B cells in most cases of the disease. Apart from...
Casola, Stefano, Cattoretti, Giorgio, Uyttersprot, Nathalie, Koralov, Sergei B., Seagal, Jane, Hao, Zhenyue, ...
Germinal centers (GCs) represent the main sites for the generation of high-affinity, class-switched antibodies during T cell-dependent antibody responses. To study gene function specifically in GC B...
Single-Cell PCR Analysis of T Helper Cells in Human Lymph Node Germinal Centers
Roers, Axel, Hansmann, Martin Leo, Rajewsky, Klaus, Küppers, Ralf
The T helper cell population of human lymph node germinal centers (GCs) was analyzed for clonality and signs of antigen selection. Frozen sections of lymph node biopsies taken from three different...
Willenbrock, Klaus, Roers, Axel, Blöhbaum, Birgit, Rajewsky, Klaus, Hansmann, Martin-Leo
A minor component (about 25%) of lymphocytes in Hodgkin’s disease (HD) are CD8+ T cells. It is unclear whether the presence of these cells reflects an antitumor cytotoxic response. The goal of the...
Schenten, Dominik, Egert, Angela, Pasparakis, Manolis, Rajewsky, Klaus
In T-cell–dependent antibody responses, antigen-specific B cells undergo a phase of secondary antibody diversification in germinal centers (GCs). Somatic hypermutation (SHM) introduces mutations...
Yin Yang 1 is a critical regulator of B-cell development
Liu, Huifei, Schmidt-Supprian, Marc, Shi, Yujiang, Hobeika, Elias, Barteneva, Natasha, Jumaa, Hassan, ...
The role of the transcription factor Yin Yang 1 (YY1) in development is largely unknown. Here we show that specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the...
Waisman, Ari, Kraus, Manfred, Seagal, Jane, Ghosh, Snigdha, Melamed, Doron, Song, Jian, ...
We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin (Ig) γ1 or μ heavy chains. Progenitor cells expressing γ1 chains from the...
Direct in vivo VH to JH rearrangement violating the 12/23 rule
Koralov, Sergei B., Novobrantseva, Tatiana I., Hochedlinger, Konrad, Jaenisch, Rudolf, Rajewsky, Klaus
V(D)J recombination at the immunoglobulin heavy chain (IgH) locus follows the 12/23 rule to ensure the correct assembly of the variable region gene segments. Here, we report characterization of an in...
Hao, Zhenyue, Hampel, Brigitte, Yagita, Hideo, Rajewsky, Klaus
To study the role of Fas–Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through...
Roers, Axel, Siewe, Lisa, Strittmatter, Elke, Deckert, Martina, Schlüter, Dirk, Stenzel, Werner, ...
Interleukin (IL)-10 is a regulator of inflammatory responses and is secreted by a variety of different cell types including T cells. T regulatory cells have been shown to suppress immune responses by...
Reichlin, Amy, Gazumyan, Anna, Nagaoka, Hitoshi, Kirsch, Kathrin H., Kraus, Manfred, Rajewsky, Klaus, ...
B cell receptor (BCR) signaling is mediated through immunoglobulin (Ig)α and Igβ a membrane-bound heterodimer. Igα and Igβ are redundant in their ability to support early B cell development, but...
Aberrant T cell differentiation in the absence of Dicer
Muljo, Stefan A., Ansel, K. Mark, Kanellopoulou, Chryssa, Livingston, David M., Rao, Anjana, Rajewsky, Klaus
Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and...
The BCL2A1 gene as a pre–T cell receptor–induced regulator of thymocyte survival
Mandal, Malay, Borowski, Christine, Palomero, Teresa, Ferrando, Adolfo A., Oberdoerffer, Philipp, Meng, Fanyong, ...
The pre–T cell receptor (TCR) is expressed early during T cell development and imposes a tight selection for differentiating T cell progenitors. Pre-TCR–expressing cells are selected to survive...
Oberdoerffer, Philipp, Novobrantseva, Tatiana I., Rajewsky, Klaus
Immunoglobulin light chain (IgL) rearrangements occur more frequently at Igκ than at Igλ. Previous results suggested that the unrearranged Igκ locus negatively regulates Igλ transcription and/or...
Silencing of B Cell Receptor Signals in Human Naive B Cells
Feldhahn, Niklas, Schwering, Ines, Lee, Sanggyu, Wartenberg, Maria, Klein, Florian, Wang, Hui, ...
To identify changes in the regulation of B cell receptor (BCR) signals during the development of human B cells, we generated genome-wide gene expression profiles using the serial analysis of gene...
IκB Kinase Signaling Is Essential for Maintenance of Mature B Cells
Pasparakis, Manolis, Schmidt-Supprian, Marc, Rajewsky, Klaus
Nuclear factor (NF)-κB proteins play crucial roles in immune responses and cellular survival. Activation of NF-κB is mediated by the IκB kinase (IKK) complex, which is composed of two kinases,...
Effective Destruction of Fas-deficient Insulin-producing β Cells in Type 1 Diabetes
Apostolou, Irina, Hao, Zhenyue, Rajewsky, Klaus, Von Boehmer, Harald
In type 1 diabetes, autoimmune T cells cause destruction of pancreatic β cells by largely unknown mechanism. Previous analyses have shown that β cell destruction is delayed but can occur in...
Endres, Robert, Alimzhanov, Marat B., Plitz, Thomas, Fütterer, Agnes, Kosco-Vilbois, Marie H., Nedospasov, Sergei A., ...
The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF),...
Novobrantseva, Tatiana I., Martin, Verena M., Pelanda, Roberta, Müller, Werner, Rajewsky, Klaus, Ehlich, Andreas
In mouse mutants incapable of expressing μ chains, VκJκ joints are detected in the CD43+ B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis...
The Toll-like Receptor Protein Rp105 Regulates Lipopolysaccharide Signaling in B Cells
Ogata, Hirotaka, Su, I-hsin, Miyake, Kensuke, Nagai, Yoshinori, Akashi, Sachiko, Mecklenbräuker, Ingrid, ...
The susceptibility to infections induced by Gram-negative bacteria is largely determined by innate immune responses to bacteria cell wall lipopolysaccharide (LPS). The stimulation of B cells by LPS...
DETERMINATION OF ANTIBODY CLASS IN A SYSTEM OF COOPERATING ANTIGENIC DETERMINANTS
Schirrmacher, Volker, Rajewsky, Klaus
19S and 7S memory is analyzed in a system of cooperating antigenic determinants. Cooperation occurs in the induction of both 19S and 7S secondary antibodies, and for both responses carrier...
Babbe, Holger, Roers, Axel, Waisman, Ari, Lassmann, Hans, Goebels, Norbert, Hohlfeld, Reinhard, ...
Clonal composition and T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at...
Bräuninger, Andreas, Spieker, Tilmann, Willenbrock, Klaus, Gaulard, Philippe, Wacker, Hans-Heinrich, Rajewsky, Klaus, ...
Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a peculiar T cell lymphoma, as expanding B cell clones are often present besides the malignant T cell clones. In addition, large...
Kraus, Manfred, Pao, Lily I., Reichlin, Amy, Hu, Yun, Canono, Beth, Cambier, John C., ...
To determine the function of immunoglobulin (Ig)α immunoreceptor tyrosine–based activation motif (ITAM) phosphorylation, we generated mice in which Igα ITAM tyrosines were replaced by...
Homeostasis of Peripheral B Cells in the Absence of B Cell Influx from the Bone Marrow
To study homeostasis of peripheral B lymphocytes in the absence of B cell influx from the bone marrow, we generated a mouse mutant in which the recombination-activating gene (RAG)-2 can be inducibly...
Lam, Kong-Peng, Rajewsky, Klaus
Mice expressing the immunoglobulin (Ig) heavy (H) chain variable (V) region from a rearranged VH12 gene inserted into the IgH locus generate predominantly B-1 cells, whereas expression of two other...
Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma
Jungnickel, Berit, Staratschek-Jox, Andrea, Bräuninger, Andreas, Spieker, Tilmann, Wolf, Jürgen, Diehl, Volker, ...
Members of the nuclear factor (NF)-κB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the...
Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma
Müschen, Markus, Rajewsky, Klaus, Bräuninger, Andreas, Baur, Audrey Sylvia, Oudejans, Joost J., Roers, Axel, ...
Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously...
Reichlin, Amy, Hu, Yun, Meffre, Eric, Nagaoka, Hitoshi, Gong, Shiaoching, Kraus, Manfred, ...
The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig)α and Igβ, a pair of membrane-bound Ig superfamily proteins, each of which contains a single...
Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair–deficient Mice
Jacobs, Heinz, Fukita, Yosho, De Boer, Jan, Weeda, Geert, Essers, Jeroen, ...
To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency,...
Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching
Manis, John P., Gu, Yansong, Lansford, Rusty, Sonoda, Eiichiro, Ferrini, Roger, Davidson, Laurie, ...
Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required...
Betz, Ulrich A.K., Bloch, Wilhelm, Van Den Broek, Maries, Yoshida, Kanji, Taga, Tetsuya, Kishimoto, Tadamitsu, ...
The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1...
Klein, Ulf, Rajewsky, Klaus, Küppers, Ralf
Immunoglobulin (Ig)M+IgD+ B cells are generally assumed to represent antigen-inexperienced, naive B cells expressing variable (V) region genes without somatic mutations. We report here that human...
Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction
Müschen, Markus, Re, Daniel, Jungnickel, Berit, Diehl, Volker, Rajewsky, Klaus, Küppers, Ralf
Somatic hypermutation specifically modifies rearranged immunoglobulin (Ig) genes in germinal center (GC) B cells. However, the bcl-6 gene can also acquire somatic mutations during the GC reaction,...
Fehr, Thomas, Rickert, Robert C., Odermatt, Bernhard, Roes, Jürgen, Rajewsky, Klaus, Hengartner, Hans, ...
Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail...
The Molecular Mechanism of B Cell Activation by toll-like Receptor Protein RP-105
Chan, Vivien W.F., Mecklenbräuker, Ingrid, Su, I-hsin, Texido, Gemma, Leitges, Michael, Carsetti, Rita, ...
The B cell–specific transmembrane protein RP-105 belongs to the family of Drosophila toll-like proteins which are likely to trigger innate immune responses in mice and man. Here we demonstrate that...
Bourgeois, Christine, Hao, Zhenyue, Rajewsky, Klaus, Potocnik, Alexandre J., Stockinger, Brigitta
A model of chemical thymectomy by inducible Rag ablation was used to study peripheral T cell homeostasis. Induction of Rag ablation was efficient and complete, leading to cessation of thymic T cell...
Sasaki, Yoshiteru, Calado, Dinis P., Derudder, Emmanuel, Zhang, Baochun, Shimizu, Yuri, Mackay, Fabienne, ...
BAFF-R-dependent activation of the alternative NF-κB pathway plays an essential role in mature B cell survival. Mutations leading to overexpression of NIK and deletion of the TRAF3 gene are...
BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells
Otipoby, Kevin L., Sasaki, Yoshiteru, Schmidt-Supprian, Marc, Patke, Alina, Gareus, Ralph, Pasparakis, Manolis, ...
B cell activating factor (BAFF) signals through BAFF-R to promote mature B cell survival. Recent analyses of BAFF-induced signaling revealed direct association between augmented B cell metabolic...
Hair Loss and Defective T- and B-Cell Function in Mice Lacking ORAI1▿ †
Gwack, Yousang, Srikanth, Sonal, Oh-hora, Masatsugu, Hogan, Patrick G., Lamperti, Edward D., Yamashita, Megumi, ...
ORAI1 is a pore subunit of the store-operated Ca2+ release-activated Ca2+ (CRAC) channel. To examine the physiological consequences of ORAI1 deficiency, we generated mice with targeted disruption of...
Generation of mice with a conditional Foxp2 null allele
French, Catherine A, Groszer, Matthias, Preece, Christopher, Coupe, Anne-Marie, Rajewsky, Klaus, Fisher, Simon E
Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is...
Wang, Jing H., Alt, Frederick W., Gostissa, Monica, Datta, Abhishek, Murphy, Michael, Alimzhanov, Marat B., ...
Nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch...
Schenten, Dominik, Kracker, Sven, Esposito, Gloria, Franco, Sonia, Klein, Ulf, Murphy, Michael, ...
Polζ is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible...
PLC-γ2 is essential for formation and maintenance of memory B cells
Hikida, Masaki, Casola, Stefano, Takahashi, Noriko, Kaji, Tomohiro, Takemori, Toshitada, Rajewsky, Klaus, ...
Resting antigen-experienced memory B cells are thought to be responsible for the more rapid and robust antibody responses after antigen reencounter, which are the hallmark of memory humoral...
Requirement for balanced Ca/NFAT signaling in hematopoietic and embryonic development
Müller, Martin R., Sasaki, Yoshiteru, Stevanovic, Irena, Lamperti, Edward D., Ghosh, Srimoyee, Sharma, Sonia, ...
NFAT transcription factors are highly phosphorylated proteins residing in the cytoplasm of resting cells. Upon dephosphorylation by the phosphatase calcineurin, NFAT proteins translocate to the...