Cellular origin of human B-cell lymphomas

New England Journal of Medicine

Volumn 341, Issue 20, 1999, Pages 1520-1529

  Küppers, Ralf ^a   Klein, Ulf ^a   Hansmann, Martin Leo ^b   Rajewsky, Klaus ^a  

^a UNIVERSITY OF COLOGNE   (Germany)

^b GOETHE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY SPECIFICITY; ARTICLE; B CELL LYMPHOMA; CARCINOGENESIS; CELL MATURATION; CELL SELECTION; GERMINAL CENTER; HUMAN; HUMAN CELL; IMMUNOPHENOTYPING; NONHODGKIN LYMPHOMA; PRIORITY JOURNAL;

B-LYMPHOCYTES; CELL TRANSFORMATION, NEOPLASTIC; EPITOPES, B-LYMPHOCYTE; GENE REARRANGEMENT, B-LYMPHOCYTE; GERMINAL CENTER; HUMANS; IMMUNOGLOBULIN CLASS SWITCHING; IMMUNOGLOBULIN VARIABLE REGION; LYMPHOCYTE COOPERATION; LYMPHOMA, B-CELL; TRANSLOCATION, GENETIC;

EID: 0033547310     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM199911113412007     Document Type: Article

References (90)

1. Tonegawa S. Somatic generation of antibody diversity. Nature 1983; 302:575-81.
2. Rajewsky K. Clonal selection and learning in the antibody system. Nature 1996;381:751-8.
3. Lam KP, Kühn R, Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 1997;90:1073-83.
4. Nussenzweig MC. Immune receptor editing: revise and select. Cell 1998;95:875-8.
5. Goossens T, Klein U, Küppers R. Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease. Proc Natl Acid Sci U S A 1998;95: 2463-8.
6. Wilson PC, de Bouteiller O, Liu YJ, et al. Somatic hypermutation introduces insertions and deletions into immunoglobulin V genes. J Exp Med 1998;187:59-70.
7. Meffre E, Papavasiliou F, Cohen P, et al. Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells. J Exp Med 1998;188:765-72.
8. Han S, Dillon SR, Zheng B, Shimoda M, Schlissel MS, Kelsoe G. V(D)J recombinase activity in a subset of germinal center B lymphocytes. Science 1997;278:301-5.
9. Liu YJ, Arpin C, de Bouteiller O, et al. Sequential triggering of apoptosis, somatic mutation and isotype switch during germinal center development. Semin Immunol 1996,8:169-77.
10. Klein U, Rajewsky K, Küppers R. 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. J Exp Med 1998;188: 1679-89.
11. Stall AM, Wells SM, Lam KP. B-1 cells: unique origins and functions. Semin Immunol 1996;8:45-59.
12. Brezinschek HP, Foster SJ, Brezinschek RI, DörnerT, Domiati-Saad R, Lipsky PE. Analysis of the human VH gene repertoire: differential effects of selection and somatic hypermutation on human peripheral CD5(+)/IgM+ and CD5(-)/IgM+ B cells. J Clin Invest 1997;99:2488-501.
13. Fischer M, Klein U, Küppers R. Molecular single-cell analysis reveals that CD5-positive peripheral blood B cells in healthy humans are characterized by rearranged Vkappa genes lacking somatic mutation. J Clin Invest 1997;100:1667-76.
14. Küppers R, Zhao M, Hansmann ML, Rajewsky K. Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J 1993;12:4955-67.
15. Jacob J, Kelsoe G, Rajewsky K, Weiss U. Intraclonal generation of antibody mutants in germinal centres. Nature 1991;354:389-92.
16. Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev 1992;3:101-21.
17. Razanajaona D, van Kooten C, Lebecque S, et al. Somatic mutations in human Ig variable genes correlate with a partially functional CD40-lig- and in the X-linked hyper-IgM syndrome. J Immunol 1996;157:1492-8.
18. Agematsu K, Nagumo H, Yang FC, et al. B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production. Eur J Immunol 1997;27:2073-9.
19. Tangye SG, Liu YJ, Aversa G, Phillips JH, de Vries JE. Identification of functional human splenic memory B cells by expression of CD148 and CD27. J Exp Med 1998;188:1691-703.
20. van Es JH, Meyling FH, Logtenberg T. High frequency of somatically mutated IgM molecules in the human adult blood B cell repertoire. Eur J Immunol 1992;22:2761-4.
21. Huang C, Stewart AK, Schwartz RS, Stollar BD. Immunoglobulin heavy chain gene expression in peripheral blood B lymphocytes. J Clin Invest 1992;89:1331-43.
22. Pascual V, Liu YJ, Magalski A, de Bouteiller O, Banchereau J, Capra JD. Analysis of somatic mutation in five B cell subsets of human tonsil. J Exp Med 1994;180:329-39.
23. Klein U, Küppers R, Rajewsky K. Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express V kappa genes with no or little somatic mutation throughout life. Eur J Immunol 1993;23:3272-7.
24. Mortari F, Wang JY, Schroeder HW Jr. Human cord blood antibody repertoire: mixed population of VH gene segments and CDR3 distribution in the expressed C alpha and C gamma repertoires. J Immunol 1993;1 50: 1348-57.
25. Klein U, Goossens T, Fischer M, et al, Somatic hypermutation in normal and transformed human B cells. Immunol Rev 1998;162:261-80.
26. Brezinschek HP, Brezinschek RI, Lipsky PE. Analysis of the heavy chain repertoire of human peripheral B cells using single-cell polymerase chain reaction. J Immunol 1995;155:190-202.
27. Jelinek DF, Splawski JB, Lipsky PE. Human peripheral blood B lymphocyte subpopulations: functional and phenotypic analysis of surface IgD positive and negative subsets. J Immunol 1986;136:83-92.
28. Klein U, Küppers R, Rajewsky K. Evidence for a large compartment of IgM-expressing memory B cells in humans. Blood 1997;89:1288-98.
29. Brandtzaeg P, Halstensen TS, Kett K, et al. Immunobiology and immunopathology of human gut mucosa: humoral immunity and intraepithelial lymphocytes. Gastroenterology 1989;97:1562-84.
30. Dunn-Walters DK, Boursier L, Spencer J. Hypermutation, diversity and dissemination of human intestinal lamina propria plasma cells. Eur J Immunol 1997;27:2959-64.
31. Fischer M, Küppers R. Human IgA- and IgM-secreting intestinal plasma cells carry heavily mutated VH region genes. Eur J Immunol 1998;28. 2971-7.
32. Bahler DW, Campbell MJ, Hart S, Miller RA, Levy S, Levy R. Ig VH gene expression among human follicular lymphomas. Blood 1991;78: 1561-8.
33. Cleary ML, Meeker TC, Levy S, et al. Clustering of extensive somatic mutations in the variable region of an immunoglobulin heavy chain gene from a human B cell lymphoma. Cell 1986;44:97-106.
34. Chapman CJ, Mockridge CI, Rowe M, Rickinson AB, Stevenson FK. Analysis of VH genes used by neoplastic B cells in endemic Burkitt's lymphoma shows somatic hypermutation and intraclonal heterogeneity. Blood 1995;85:2176-81.
35. Klein U, Klein G, Ehlin-Henriksson B, Rajewsky K, Küppers R. Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes. Mol Med 1995;1:495-505.
36. Tamaru J, Hummel M, Marafioti T, et al. Burkitt's lymphomas express VH genes with a moderate number of antigen-selected somatic mutations. Am J Pathol 1995;147:1398-407.
37. Ng VL, Hurt MH, Fein CL, et al. IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis. Blood 1994;83:1067-78. [Erratum, Blood 1994;84:995.]
38. Riboldi P, Gaidano G, Schettino EW, et al. Two acquired immunodeficiency syndrome-associated Burkitt's lymphomas produce specific anti-i IgM cold agglutinins using somatically mutated VH4-21 segments. Blood 1994;83:2952-61.
39. Hsu FJ, Levy R. Preferential use of the VH4 Ig gene family by diffuse large-cell lymphoma. Blood 1995;86:3072-82.
40. Küppers R, Rajewsky K, Hansmann ML. Difluse large cell lymphomas arc derived from mature B cells carrying V region genes with a high load of somatic mutation and evidence of selection for antibody expression. Eur J Immunol 1997;27:1398-405.
41. Bräuninger A, Küppers R, Spieker T, et al. Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells. Blood 1999;93:2679-87.
42. Tierens A, Delabie J, Pittaluga S, Driessen A, DeWolf-Peeters C. Mutation analysis of the rearranged immunoglobuiin heavy chain genes of marginal zone cell lymphomas indicates an origin from different marginal zone B lymphocyte subsets. Blood 1998;91:2381-6.
43. Bahler DW, Miklos JA, Swerdlow SH. Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid tissue-type lymphomas. Blood 1997;89:3335-44.
44. Du M, Diss TC, Xu C, Peng H, Isaacson PG, Pan L. Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the donal expansion. Leukemia 1996;10:1190-7.
45. Küppers R, Hajadi M, Plank L, Rajewsky K, Hansmann ML. Molecular Ig gene analysis reveals that monocytoid B cell lymphoma is a malignancy of mature B cells carrying somatically mutated V region genes and suggests that rearrangement of the kappa-deleting element (resulting in deletion of the Ig kappa enhancers) abolishes somatic hypermutation in the human. Eur J Immunol 1996;26:1794-800.
46. Qin Y, Greiner A, Hallas C, Haedicke W, Müller-Hermelink HK. Intraclonal offspring expansion of gastric low-grade MALT-type lymphoma: evidence for the role of antigen-driven high-affinity mutation in lympho-magenesis. Lab Invest 1997;76;477-85.
47. Zhu D, Oscier DG, Stevenson FK. Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes. Blood 1995;85:1603-7
48. Davi F, Maloum K, Michel A, et al. High frequency of somatic mutations in the VH genes expressed in prolymphocytic leukemia. Blood 1996; 88:3953-61.
49. Wagner SD, Martinelli V, Luzzatto L. Similar patterns of V kappa gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstrom's macroglobulinemia, and myeloma. Blood 1994;83:3647-53.
50. Ivanovski M, Silvestri F, Pozzato G, et al. Somatic hypermutation, clonal diversity, and preferential expression of the VH 51p1/VL kv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas. Blood 1998;91:2433-42.
51. Aarts WM, Willemze R, Bende RJ, Meijer CJLM, Pals ST, van Noesel CJM. VH gene analysis of primary cutaneous B-cell lymphomas: evidence for ongoing somatic hypermutation and isotype switching. Blood 1998;92: 3857-64.
52. Fais F, Ghiotto F, Hashimoto S, et al. Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest 1998;102:1515-25.
53. Baker BW, Deane M, Gilleece MH, Johnston D, Scarffe JH, Norton JD. Distinctive features of immunoglobulin heavy chain variable region gene rearrangement in multiple myeloma. Leuk Lymphoma 1994;14:291-301.
54. Bakkus MH, Heirman C, Van Riet I, Van Camp B, Thielemans K. Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. Blood 1992;80:2326-35.
55. Bahler DW, Levy R. Clonal evolution of a follicular lymphoma: evidence for antigen selection, Proc Natl Acad Sci U S A 1992;89:6770-4.
56. Chapman CJ, Zhou JX, Gregory C, Rickinson AB, Stevenson FK. VH and VL gene analysis in sporadic Burkitt's lymphoma shows somatic hypermutation, intraclonal heterogeneity, and a role for antigen selection. Blood 1996;88:3562-8.
57. Sale JE, Neuberger MS. TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line. Immunity 1998;9:859-69.
58. Ottensmeier CH, Thompsett AR, Zhu D, Wilkins BS, Sweetenham JW, Stevenson FK. Analysis of VH genes in follicular and diffuse lymphoma shows ongoing somatic mutation and multiple isotype transcripts in early disease with changes during disease progression. Blood 1998;91: 4292-9.
59. Hummel M, Tamaru J, Kalvelage B, Stein H. Mantle cell (previously centrocytic) lymphomas express VH genes with no or very little somatic mutations like the physiologic cells of the follicle mantle. Blood 1994;84: 403-760.
60. Hayakawa K, Hardy RR, Stall AM, Herzenbcrg LA, Herzenbcrg LA. Immunoglobulin-bearing B cells reconstitute and maintain the murine Ly-I B cell lineage. Eur J Immunol 1986;16:1313-6.
61. Kocks C, Rajewsky K. Stable expression and somatic hypermutation of antibody V regions in B-cell developmental pathways. Annu Rev Immunol 1989;7:537-59.
62. Küppers R, Rajewsky K. The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annu Rev Immunol 1998;16:471-93.
63. Kanzler H, Küppers R, Hansmann ML, Rajewsky K. Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 1996;184:1495-505.
64. Braeuninger A, Küppers R, Strickler JG, Wacker HH, Rajewsky K, Hansmann ML. Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proc Natl Acad Sci U S A 1997;94:9337-42. [Erratum, Proc Natl Acad Sci U S A 1997;94:14211.]
65. Hummel M, Marafioti T, Stein H. Immunoglobulin V genes in Reed-Sternberg cells. N Engl J Med 1996;334:405-6.
66. Ohno T, Stribley JA, Wu G, Hinrichs SH, Weisenburger DD, Chan WC. Clonality in nodular lymphocyte-predominant Hodgkin's disease. N Engl J Med 1997;337:459-65.
67. Marafioti T, Hummel M, Anagnostopoulos I, et al. Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med 1997;337:453-8.
68. Küppers R, Rajewsky K, Zhao M, et al. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci U S A 1994;91: 10962-6.
69. Braüninger A, Hansmann, M-L, Strickler JG, et al. Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma. N Engl J Med 1999; 340:1239-47
70. Jox A, Zander T, Küppers R, et al. Somatic mutations within the untranslated regions of rearranged Ig genes in a case of classical Hodgkin's disease as a potential cause for the absence of Ig in the lymphoma cells. Blood 1999;93:3964-72.
71. Davis TH, Morton CC, Miller-Cassman R, Balk SP, Kadin ME. Hodgkin's disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone. N EngL J Med 1992;326: 1115-22.
72. Magrath I. The pathogenesis of Burkitt's lymphoma. Adv Cancer Res 1990;55:133-270.
73. Ye BH, Chaganti S, Chang CC, et al. Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma. EMBO J 1995;14:6209-17.
74. Chesi M, Nardini E, Brents LA, et al. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Genet 1997;16:260-4.
75. Hiom K, Melek M, GelLert M. DNA transposition by RAG1 and RAG2 proteins: a possible source of oncogenic translocations. Cell 1998; 94:463-70.
76. AgrawaL A, Eastman QM, Schatz DG. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 1998;394:744-51.
77. Pasqualucci L, Migliazza A, Fracchiolla N, et al. BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci. Proc Natl Acad Sci U S A 1998;95:11816-21.
78. Shen HM, Peters A, Baron B, Zhu X, Storb U. Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 1998;280:1750-2.
79. Migliazza A, Martinotti S, Chen W, et al. Frequent somatic hypermutation of the 5′ noncoding region of the BCL6 gene in B-cell lymphoma. Proc Natl Acad Sci U S A 1995;92:12520-4.
80. Hoang AT, Lutterbach B, Lewis BC, et al. A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-myc transactivation domain. Mol Cell Biol 1995;15:4031-42.
81. Hussell T, Isaacson PG, Crabtrce JE, Spencer J. Helicobacter pylori-specific tumour-infiltrating T cells provide contact dependent help for the growth of malignant B cells in low-grade gastric lymphoma of mucosa-associated lymphoid tissue. J Pathol 1996;178:122-7.
82. Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori. Lancet 1993;342:575-7.
83. Vaandrager IW, Schuuring E, Kluin-Nelemans HC, Dyer MJS, Raap AK, Kluin PM. DNA fiber fluorescence in situ hybridization analysis of immunoglobulin class switching in B-cell neoplasia: aberrant CH gene rearrangements in follicle center-cell lymphoma. Blood 1998;92:2871-8.
84. van den Berg A, Visser L, Poppema S. High expression of the CC chemokine TARC in Reed-Stern berg cells: a possible explanation for the characteristic T-cell infiltrate in Hodgkin's lyphoma. Am J Pathol 1999;154: 1685-91.
85. Kapp U, Yeh WC, Patterson B, et al. Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells. J Exp Med 1999;189:1939-46.
86. Cossman J, Messineo C, Bagg A. Reed-Sternberg cell: survival in a hostile sea. Lab Invest 1998;78:229-35.
87. Poetsch M, Weber-Matthiesen K, Plendl HJ, Grote W, Schlegelberger B. Detection of the t(14;18) chromosomal translocation by interphase cytogenetics with yeast-artificial-chromosome probes on follicular lymphoma and nonneoplastic lymphoproliferation. J Clin Oncol 1996;14:963-9.
88. Gaidano G, Dalla-Favera R. The biology of high-grade non-Hodgkin's lymphomas. In: Cannellos GP, Lister TA, Sklar JL, eds. The lymphomas. Philadelphia: W.B. Saunders, 1998:353-67.
89. Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood 1998;91:3-21.
90. Niedobitek G, Young LS, Herbst H. Epstein-Barr virus infection and the pathogenesis of malignant lymphomas. Cancer Surv 1997;30:143-62.