Ralf Küppers

Frequent occurrence of deletions and duplications during somatic hypermutation: Implications for oncogene translocations and heavy chain disease

Goossens, Tina, Klein, Ulf, Küppers, Ralf

Human naive and germinal center (GC) B cells were sorted by flow cytometry and rearranged VH region genes were amplified and sequenced from single cells. Whereas no deletions or insertions were found...

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...

BCL-6 mutations in normal germinal center B cells: Evidence of somatic hypermutation acting outside Ig loci

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...

Hodgkin and Reed–Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells

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)...

Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling

Küppers, Ralf, Klein, Ulf, Schwering, Ines, Distler, Verena, Bräuninger, Andreas, Cattoretti, Giorgio, ...

Hodgkin lymphoma (HL) is a malignancy of unknown pathogenesis. The malignant Hodgkin and Reed/Sternberg (HRS) cells derive from germinal center B cells (or rarely, T cells) but have a heterogeneous...

Epstein–Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction

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...

Profiling of Hodgkin’s Lymphoma Cell Line L1236 and Germinal Center B Cells: Identification of Hodgkin’s Lymphoma–specific Genes

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...

Frequent occurrence of deletions and duplications during somatic hypermutation: Implications for oncogene translocations and heavy chain disease

Goossens, Tina, Klein, Ulf, Küppers, Ralf

Human naive and germinal center (GC) B cells were sorted by flow cytometry and rearranged VH region genes were amplified and sequenced from single cells. Whereas no deletions or insertions were found...

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...

BCL-6 mutations in normal germinal center B cells: Evidence of somatic hypermutation acting outside Ig loci

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...

Hodgkin and Reed–Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells

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)...

Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling

Küppers, Ralf, Klein, Ulf, Schwering, Ines, Distler, Verena, Bräuninger, Andreas, Cattoretti, Giorgio, ...

Hodgkin lymphoma (HL) is a malignancy of unknown pathogenesis. The malignant Hodgkin and Reed/Sternberg (HRS) cells derive from germinal center B cells (or rarely, T cells) but have a heterogeneous...

Epstein–Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction

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...

Profiling of Hodgkin’s Lymphoma Cell Line L1236 and Germinal Center B Cells: Identification of Hodgkin’s Lymphoma–specific Genes

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...

Absence of Immunoglobulin Class Switch in Primary Lymphomas of the Central Nervous System

Montesinos-Rongen, Manuel, Schmitz, Roland, Courts, Cornelius, Stenzel, Werner, Bechtel, Dörte, Niedobitek, Gerald, ...

Primary lymphomas of the central nervous system (PCNSLs) were investigated for their capacity to perform further maturation steps. We studied a series of 11 PCNSLs derived from immunocompetent...

Aberrant Expression of ID2, a Suppressor of B-Cell-Specific Gene Expression, in Hodgkin’s Lymphoma

Renné, Christoph, Martin-Subero, Jose Ignacio, Eickernjäger, Maren, Hansmann, Martin-Leo, Küppers, Ralf, Siebert, Reiner, ...

The global loss of B-cell-specific gene expression is a distinctive feature of the Hodgkin-Reed/Sternberg (HRS) cells of classical Hodgkin’s lymphoma (HL). The reasons for this loss remained...

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...

Primary Central Nervous System Lymphomas Are Derived from Germinal-Center B Cells and Show a Preferential Usage of the V4–34 Gene Segment

Montesinos-Rongen, Manuel, Küppers, Ralf, Schlüter, Dirk, Spieker, Tilmann, Van Roost, Dirk, Schaller, Carlo, ...

Primary central nervous system lymphomas (PCNSLs) have recently received considerable clinical attention due to their increasing incidence. To clarify the histogenetic origin of these intriguing...

Analysis of T-Cell Subpopulations in T-Cell Non-Hodgkin’s Lymphoma of Angioimmunoblastic Lymphadenopathy with Dysproteinemia Type by Single Target Gene Amplification of T Cell Receptor- β Gene Rearrangements

Willenbrock, Klaus, Roers, Axel, Seidl, Christian, Wacker, Hans-Heinrich, Küppers, Ralf, Hansmann, Martin-Leo

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is defined in the current lymphoma classifications as a T-cell non-Hodgkin’s lymphoma. However, in approximately one third of the cases...

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...

Survival and Clonal Expansion of Mutating “Forbidden” (Immunoglobulin Receptor–Deficient) Epstein-Barr Virus–Infected B Cells in Angioimmunoblastic T Cell Lymphoma

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...

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...

Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells

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,...

Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis

Brune, Verena, Tiacci, Enrico, Pfeil, Ines, Döring, Claudia, Eckerle, Susan, ...

The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of...

TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma

Schmitz, Roland, Hansmann, Martin-Leo, Bohle, Verena, Martin-Subero, Jose Ignacio, Hartmann, Sylvia, Mechtersheimer, Gunhild, ...

Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor κB (NF-κB)....