Cellular Origin of Human B-Cell Lymphomas

doi:10.1056/NEJM199911113412007

Volume 341:1520-1529		November 11, 1999		Number 20

Cellular Origin of Human B-Cell Lymphomas

Ralf Küppers, Ph.D., Ulf Klein, Ph.D., Martin-Leo Hansmann, M.D., and Klaus Rajewsky, M.D.

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The origin of human lymphomas has been studied by various approaches,including histology and immunophenotyping. In some types oflymphoma these studies suggested the cellular origin, but inmany instances the origin could not be identified. When somaticmutations of the genes for the variable region of the B-lymphocyteantigen receptor proved to be a hallmark of germinal-centerB cells and their descendants, sequence analysis of the variable-regiongenes of B-cell lymphomas offered a molecular approach to studyingthe origin of the tumors. Before discussing the results of thesestudies, we outline the human peripheral B-cell repertoire andits generation.

The Human Peripheral B-Cell Repertoire and Its Generation

Antibody Specificity and Selection of B Cells

. . . [Full Text of this Article]

Genetic Changes in B Cells within Germinal Centers

The Peripheral B-Cell Repertoire in Humans

Precursors of Human B-Cell Lymphomas

Non-Hodgkin's Lymphomas

Hodgkin's Disease

The Role of Germinal Centers in the Pathogenesis of B-Cell Tumors

Transforming Events as Byproducts of B-Cell Differentiation in the Germinal Center

Dependence of B-Cell Lymphomas on the Expression of Antigen Receptors and the Microenvironment

The Diversity of Human B-Cell Lymphomas

Conclusions

Source Information

From the Institute for Genetics (R.K., U.K., K.R.) and the Department of Internal Medicine (R.K.), University of Cologne, Cologne; and the Department of Pathology, University of Frankfurt, Frankfurt (M.-L.H.) — both in Germany.

Address reprint requests to Dr. Küppers at the University of Cologne, Department of Internal Medicine, LFI E4 R706, Joseph-Stelzmannstr. 9, 50931 Cologne, Germany, or at rkuppers@mac.genetik.uni-koeln.de.

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Wang, C.-X., Wadehra, M., Fisk, B. C., Goodglick, L., Braun, J. (2001). Epithelial membrane protein 2, a 4-transmembrane protein that suppresses B-cell lymphoma tumorigenicity. Blood 97: 3890-3895 [Abstract] [Full Text]
van Kemenade, F. J., Raaphorst, F. M., Blokzijl, T., Fieret, E., Hamer, K. M., Satijn, D. P. E., Otte, A. P., Meijer, C. J. L. M. (2001). Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood 97: 3896-3901 [Abstract] [Full Text]
Theil, J., Laumen, H., Marafioti, T., Hummel, M., Lenz, G., Wirth, T., Stein, H. (2001). Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood 97: 3191-3196 [Abstract] [Full Text]
Matsuo, K., Suzuki, R., Hamajima, N., Ogura, M., Kagami, Y., Taji, H., Kondoh, E., Maeda, S., Asakura, S., Kaba, S., Nakamura, S., Seto, M., Morishima, Y., Tajima, K. (2001). Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma. Blood 97: 3205-3209 [Abstract] [Full Text]
Du, M.-Q., Liu, H., Diss, T. C., Ye, H., Hamoudi, R. A., Dupin, N., Meignin, V., Oksenhendler, E., Boshoff, C., Isaacson, P. G. (2001). Kaposi sarcoma-associated herpesvirus infects monotypic (IgM{lambda}) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 97: 2130-2136 [Abstract] [Full Text]
Carbone, A., Gloghini, A., Larocca, L. M., Capello, D., Pierconti, F., Canzonieri, V., Tirelli, U., Dalla-Favera, R., Gaidano, G. (2001). Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. Blood 97: 744-751 [Abstract] [Full Text]
Stein, H., Marafioti, T., Foss, H.-D., Laumen, H., Hummel, M., Anagnostopoulos, I., Wirth, T., Demel, G., Falini, B. (2001). Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription. Blood 97: 496-501 [Abstract] [Full Text]
Rai, K. R., Dohner, H., Keating, M. J., Montserrat, E. (2001). Chronic Lymphocytic Leukemia: Case-Based Session. ASH Education Book 2001: 140-156 [Abstract] [Full Text]
Harris, N. L., Stein, H., Coupland, S. E., Hummel, M., Favera, R. D., Pasqualucci, L., Chan, W. C. (2001). New Approaches to Lymphoma Diagnosis. ASH Education Book 2001: 194-220 [Abstract] [Full Text]
Ciric, B., VanKeulen, V., Rodriguez, M., Kyle, R. A., Gertz, M. A., Pease, L. R. (2001). Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor. Blood 97: 321-323 [Abstract] [Full Text]
Muschen, M., Re, D., Jungnickel, B., Diehl, V., Rajewsky, K., Kuppers, R. (2000). Somatic Mutation of the CD95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction. J. Exp. Med. 192: 1833-1840 [Abstract] [Full Text]
Aguiar, R. C. T., Yakushijin, Y., Kharbanda, S., Salgia, R., Fletcher, J. A., Shipp, M. A. (2000). BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration. Blood 96: 4328-4334 [Abstract] [Full Text]
Odendahl, M., Jacobi, A., Hansen, A., Feist, E., Hiepe, F., Burmester, G. R., Lipsky, P. E., Radbruch, A., Dorner, T. (2000). Disturbed Peripheral B Lymphocyte Homeostasis in Systemic Lupus Erythematosus. J. Immunol. 165: 5970-5979 [Abstract] [Full Text]
De Re, V., De Vita, S., Marzotto, A., Rupolo, M., Gloghini, A., Pivetta, B., Gasparotto, D., Carbone, A., Boiocchi, M. (2000). Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus-associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor-producing cells that occur mainly in type II cryoglobulinemia. Blood 96: 3578-3584 [Abstract] [Full Text]
Attaelmannan, M., Levinson, S. S. (2000). Understanding and Identifying Monoclonal Gammopathies. Clin. Chem. 46: 1230-1238 [Abstract] [Full Text]
Willenbrock, K., Roers, A., Blohbaum, B., Rajewsky, K., Hansmann, M.-L. (2000). CD8+ T Cells in Hodgkin's Disease Tumor Tissue Are a Polyclonal Population with Limited Clonal Expansion but Little Evidence of Selection by Antigen. Am. J. Pathol. 157: 171-175 [Abstract] [Full Text]
Narducci, M. G., Pescarmona, E., Lazzeri, C., Signoretti, S., Lavinia, A. M., Remotti, D., Scala, E., Baroni, C. D., Stoppacciaro, A., Croce, C. M., Russo, G. (2000). Regulation of TCL1 Expression in B- and T-Cell Lymphomas and Reactive Lymphoid Tissues. Cancer Res. 60: 2095-2100 [Abstract] [Full Text]
Macintyre, E., Willerford, D., Morris, S. W. (2000). Non-Hodgkin's Lymphoma: Molecular Features of B Cell Lymphoma. ASH Education Book 2000: 180-204 [Abstract] [Full Text]

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