Enforced Bcl-2 expression inhibits antigen-mediated clonal elimination of peripheral B cells in an antigen dose-dependent manner and promotes receptor editing in autoreactive, immature B cells

Journal of Experimental Medicine

Volumn 186, Issue 9, 1997, Pages 1513-1522

  Lang, Julie ^a   Arnold, B ^b   Hammerling, G ^b   Harris, Alan W ^c   Korsmeyer, Stanley ^d   Russell, David ^a   Strasser, Andreas ^c   Nemazee, David ^a,e  

^a NATIONAL JEWISH MEDICAL AND RESEARCH CENTER   (United States)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; PROTEIN BCL 2;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; B LYMPHOCYTE; CELL MATURATION; CONTROLLED STUDY; IMMUNOLOGICAL TOLERANCE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSGENE; TRANSGENIC MOUSE;

ANIMALS; ANTIBODIES, ANTI-IDIOTYPIC; ANTIGENS, CD45; B-LYMPHOCYTE SUBSETS; CELL DIFFERENTIATION; CELL SURVIVAL; CLONAL DELETION; DOSE-RESPONSE RELATIONSHIP, IMMUNOLOGIC; EPITHELIAL CELLS; GENE REARRANGEMENT, B-LYMPHOCYTE, LIGHT CHAIN; H-2 ANTIGENS; HYBRIDOMAS; IMMUNOGLOBULIN KAPPA-CHAINS; IMMUNOGLOBULIN LAMBDA-CHAINS; IMMUNOGLOBULIN M; INJECTIONS, INTRAPERITONEAL; LIVER; LYMPHOCYTE COUNT; LYMPHOID TISSUE; MICE; MICE, INBRED A; MICE, INBRED C3H; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 0030694311     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.186.9.1513     Document Type: Article

References (71)

1. Cory, S. 1995. Regulation of lymphocyte survival by the bcl-2 gene family. Annu. Rev. Immunol. 13:513-543.
2. Green, D.R., and D.W. Scott. 1994. Activation-induced apoptosis in lymphocytes. Curr. Opin. Immunol. 3:476-187.
3. Krammer, P.H., I. Behrmann, P. Daniel, J. Dhein, and K.M. Debatin. 1994. Regulation of apoptosis in the immune system. Curr. Opin. Immunol. 2:279-289.
4. Thompson, C.B. 1995. Apoptosis in the pathogenesis and treatment of disease. Science (Wash. DC). 5203:1456-1462.
5. Nossal, G.J. 1994. Negative selection of lymphocytes. Cell. 2: 229-239.
6. Klinman, N.R. 1996. The "clonal selection hypothesis" and current concepts of B cell tolerance. Immunity. 3:189-195.
7. Rajewsy, K. 1996. Clonal selection and learning in the antibody system. Nature (Lond.). 381:751-758.
8. Nemazee, D., and K. Buerki. 1989. Clonal deletion of autoreactive B lymphocytes in bone marrow chimeras. Proc. Natl. Acad. Sci. USA. 20:8039-8043.
9. Hartley, S.B., M.P. Cooke, D.A. Fulcher, A.W. Harris, S. Cory, A. Basten, and C.C. Goodnow. 1993. Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death. Cell. 3:325-335.
10. Fulcher, D.A., and A. Basten. 1994. Reduced life span of anergic self-reactive B cells in a double-transgenic model. J. Exp. Med. 179:125-134.
11. Finkelman, F.D., J.M. Holmes, O.I. Dukhanina, and S.C. Morris. 1995. Cross-linking of membrane immunoglobulin D, in the absence of T cell help, kills mature B cells in vivo. J. Exp. Med. 2:515-525.
12. Cyster, J.G., S.B. Hartley, and C.C. Goodnow. 1994. Competition for follicular niches excludes self-reactive cells from the recirculating B-cell repertoire. Nature (Lond.). 6496:389-395.
13. Rathmell, J.C., M.P. Cooke, W.Y. Ho, J. Grein, S.E. Townsend, M.M. Davis, and C.C. Goodnow. 1995. GD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ T cells. Nature (Lond.). 6536:181-184.
14. Russell, D.M., Z. Dembic, G. Morahan, J.F. Miller, K. Burki, and D. Nemazee. 1991. Peripheral deletion of self-reactive B cells. Nature (Lond.). 6351:308-311.
15. Tsubata, T., M. Murakami, and T. Honjo. 1994. Antigen-receptor cross-linking induces peritoneal B-cell apoptosis in normal but not autoimmunity-prone mice. Curr. Biol. 1:8-17.
16. Murakami, M., T. Tsubata, M. Okamoto, A. Shimizu, S. Kumagai, H. Imura, and T. Honjo. 1992. Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in transgenic mice. Nature (Lond.). 6373:77-80.
17. Carsetti, R., G. Kohler, and M.C. Lamers. 1995. Transitional B cells are the target of negative selection in the B cell compartment. J. Exp. Med. 6:2129-2140.
18. Scott, D.W. 1993. Analysis of B cell tolerance in vitro. Adv. Immunol. 54:393-425.
19. Novack, D.V., and S.J. Korsmeyer. 1994. Bcl-2 protein expression during murine development. Am. J. Pathol. 1:61-73.
20. Li, Y.S., K. Hayakawa, and R.R. Hardy. 1993. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J. Exp. Med. 3: 951-960.
21. Broome, H.E., C.M. Dargan, S. Krajewski, and J.C. Reed. 1995. Expression of Bcl-2, Bcl-x, and Bax after T cell activation and IL-2 withdrawal. J. Immunol. 5:2311-2317.
22. Veis, D.J., C.L. Sentman, E.A. Bach, and S.J. Korsmeyer. 1993. Expression of the Bcl-2 protein in murine and human thymocytes and in peripheral T lymphocytes. J. Immunol. 5: 2546-2554.
23. Grillot, D.A., R. Merino, and G. Nunez. 1995. Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice. J. Exp. Med. 6:1973-1983.
24. Gonzalez-Garcia, M., R. Perez-Ballestero, L. Ding, L. Duan, L.H. Boise, C.B. Thompson, and G. Nunez. 1994. bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria. Development (Camb.). 10:3033-3042.
25. Gratiot-Deans, J., R. Merino, G. Nunez, and L.A. Turka. 1994. Bcl-2 expression during T-cell development: early loss and late return occur at specific stages of commitment to differentiation and survival. Proc. Natl. Acad. Sci. USA. 22:10685-10689.
26. Merino, R., L. Ding, D.J. Veis, S.J. Korsmeyer, and G. Nunez. 1994. Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. EMBO (Eur. Mol. Biol. Organ.) J. 3:683-691.
27. Boise, L.H., M. Gonzalez-Garcia, C.E. Postema, L. Ding, T. Lindsten, L.A. Turka, X. Mao, G. Nunez, and C.B. Thompson. 1993. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 4:597-608.
28. Cory, S., A.W. Harris, and A. Strasser. 1994. Insights from transgenic mice regarding the role of bcl-2 in normal and neoplastic lymphoid cells. Philos. Trans. R. Soc. Lond. Ser. B. Biol. Sci. 1313:289-295.
29. Strasser, A., A.W. Harris, L.M. Corcoran, and S. Cory. 1994. Bcl-2 expression promotes B-but not T-lymphoid development in scid mice. Nature (Lond.). 6470:457-460.
30. Katsumata, M., R.M. Siegel, D.C. Louie, T. Miyashita, Y. Tsujimoto, P.C. Nowell, M.I. Greene, and J.C. Reed. 1992. Differential effects of Bcl-2 on T and B cells in transgenic mice. Proc. Natl. Acad. Sci. USA. 23:11376-11380.
31. McDonnell, T.J., G. Nunez, F.M. Platt, D. Hockenberry, L. London, J.P. McKearn, and S.J. Korsmeyer. 1990. Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M-and D-expressing B-cell population. Mol. Cell. Biol. 5:1901-1907.
32. Woodland, R.T., M.R. Schmidt, J.E. Riggs, S.J. Korsmeyer, A.M. Lussier, and K.A. Gravel. 1995. Radiation-induced apoptosis is differentially regulated in primary B cells from normal mice and mice with the CBA/N X-linked immunodeficiency. J. Immunol. 7:3453-3463.
33. Gottschalk, A.R., C.L. McShan, R. Merino, G. Nunez, and J. Quintans. 1994. Physiological cell death in B lymphocytes. I. Differential susceptibility of WEHI-231 sublines to anti-Ig induced physiological cell death and lack of correlation with bcl-2 expression. Int. Immunol. 1:121-130.
34. Strasser, A., S. Whittingham, D.I. Vaux, M.L. Bath, J.M. Adams, S. Cory, and A.W. Harris. 1991. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc. Natl. Acad. Sci. USA. 19: 8661-8665.
35. Reed, J.C. 1996. A day in the life of the Bcl-2 protein: does the turnover rate of Bcl-2 serve as a biological clock for cellular lifespan regulation? Leuk. Res. 2:109-111.
36. McDonnell, T.J., N. Deane, F.M. Platt, G. Nunez, U. Jaeger, J.P. McKearn, and S.J. Korsmeyer. 1989. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1:79-88.
37. Strasser, A., A.W. Harris, D.C. Huang, P.H. Krammer, and S. Cory. 1995. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO (Eur. Mol. Biol. Organ.) J. 24:6136-6147.
38. Veis, D.J., C.M. Sorenson, J.R. Shutter, and S.J. Korsmeyer. 1993. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 2: 229-240.
39. Nakayama, K., K. Nakayama, I. Negishi, K. Kuida, Y. Shinkai, M.C. Louie, L.E. Fields, P.J. Lucas, V. Stewart, F.W. Alt, et al. 1993. Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice. Science (Wash. DC.). 5128: 1584-1588.
40. Cuende, E., J.E. Ales-Martinez, L. Ding, M. Gonzalez-Garcia ,C. Martinez, and G. Nunez. 1993. Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells. EMBO (Eur. Mol. Biol. Organ.) J. 4:1555-1560.
41. Benhamou, L.E., T. Watanabe, D. Kitamura, P.A. Cazenave, and P. Sarthou. 1994. Signaling properties of anti-immunoglobulin-resistant variants of WEHI-231 B lymphoma cells. Eur. J. Immunol. 9:1993-1999.
42. Choi, M.S., L.H. Boise, A.R. Gottschalk, J. Quintans, C.B. Thompson, and G.G. Klaus. 1995. The role of bcl-XL in CD40-mediated rescue from anti-mu-induced apoptosis in WEHI-231 B lymphoma cells. Eur. J. Immunol. 5:1352-1357.
43. Fang, W., J.J. Rivard, J.A. Ganser, T.W. LeBien, K.A. Nach, D.L. Mueller, and T.W. Behrens. 1995. Bcl-xL rescues WEHI 231 B lymphocytes from oxidant-mediated death following diverse apoptotic stimuli. J. Immunol. 1:66-75.
44. Kamesaki, H., J.A. Zwiebel, J.G. Reed, and J. Cossman. 1994. Role of bcl-2 and IL-5 in the regulation of anti-IgM-induced growth arrest and apoptosis in immature B cell lines. A cooperative regulation model for B cell clonal deletion. J. Immunol. 7:3294-3305.
45. Merino, R., D.A. Grillot, P.L. Simonian, S. Muthukkumar, W.C. Fanslow, S. Bondada, and G. Nunez. 1995. Modulation of anti-IgM-induced B cell apoptosis by Bcl-xL and CD40 in WEHI-231 cells. Dissociation from cell cycle arrest and dependence on the avidity ot the antibody-IgM receptor interaction. J. Immunol. 8:3830-3838.
46. Nisitani, S., T. Tsubata, M. Murakami, M. Okamoto, and T. Honjo. 1993. The bcl-2 gene product inhibits clonal deletion of self-reactive B lymphocytes in the periphery but not in the bone marrow. J. Exp. Med. 4:1247-1254.
47. Pulendran, B., G. Kannourakis, S. Nouri, K.G. Smith, and G.J. Nossal. 1995. Soluble antigen can cause enhanced apoptosis of germinal-centre B cells. Nature (Lond.). 6529:331-334.
48. Shokat, K.M., and C.C. Goodnow. 1995. Antigen-induced B-cell death and elimination during germinal-centre immune responses. Nature (Lond.). 6529:334-338.
49. Tiegs, S.L., D.M. Russell, and D. Nemazee. 1993. Receptor editing in self-reactive bone marrow B cells. J. Exp. Med. 4: 1009-1020.
50. Gay, D., T. Saunders, S. Camper, and M. Weigert. 1993. Receptor editing: an approach by autoreactive B cells to escape tolerance. J. Exp. Med. 4:999-1008.
51. Nemazee, D.A., and K. Burki. 1989. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature (Lond.). 6207:562-566.
52. Hartley, S.B., J. Crosbie, R. Brink, A.B. Kantor, A. Basten, and C.C. Goodnow. 1991. Elimination from peripheral lymphonid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature (Lond.). 6346:765-769.
53. Melamed, D., and D. Nemazee. 1997. Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest. Proc. Natl. Acad. Sci. USA. 94:9267-9272.
54. Hertz, M., and D. Nemazee. 1997. BCR ligation induces receptor editing in IgM+IgP-bone marrow B cells in vitro. Immunity. 4:429-436.
55. Morahan, G., F.E. Brennan, P.S. Bhathal, J. Allison, K.O. Cox, and J.F. Miller. 1989. Expression in transgenic mice of class I histocompatibility antigens controlled by the metallothionein promoter. Proc. Natl. Acad. Sci. USA. 10:3782-3786.
56. Schonrich, G., F. Momburg, M. Malissen, A.M. Schmitt-Verhulst, B. Malissen, G.J. Hammerling, and B. Arnold. 1992. Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self antigen. Int. Immunol. 5:581-590.
57. Spanopoulou, E., C.A. Roman, L.M. Corcoran, M.S. Schlissel, D.P. Silver, D. Nemazee, M.C. Nussenzweig, S.A. Shinton, R.R. Hardy, and D. Baltimore. 1994. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 9:1030-1042.
58. Lang, J., M. Jackson, L. Teyton, A. Brunmark, K. Kane, and D. Nemazee. 1996. B-cells are exquisitely sensitive to central tolerance and receptor editing induced by ultralow affinity, membrane-bound antigen. J. Exp. Med. 184:1685-1697.
59. Melamed, D., J. Keuch, K. Grabstein, A. Relink, and D. Nemazee. 1997. A functional B-cell receptor transgene allows efficient IL-7 independent maturation of B-cell precursors. J. Immunol. 159:1233-1239.
60. Bikah, G., J. Carey, J.R. Ciallella, A. Tarakhovsky, and S. Bondada. 1996. CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells. Science (Wash. DC). 5294:1906-1909.
61. Steller, H. 1995 Mechanisms and genes of cellular suicide. Science (Wash. DC). 267:1445-1449.
62. Oltvai, Z.N., C.L. Milliman, and S.J. Korsmeyer. 1993. Bcl-2 heterodimerizes in vivo with a conserved homolog. Bax that accelerates programmed cell death. Cell. 4:609-619
63. Yin, X.M., Z.N. Oltvai, and S.J. Korsmeyer. 1995. Heterodimerization with Bax is required for Bcl-2 to repress cell death. Curr. Top. Microbiol. Immunol. 194:331-338.
64. Yang, E., J. Zha, J. Jockel, L.H. Boise, C.B. Thompson, and S.J. Korsmeyer, 1995. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 2: 285-291.
65. Haldar, S., N. Jena, and C.M. Croce. 1995. Inactivation of Bcl-2 by phosphorylation. Proc. Natl. Acad. Sci. USA. 10:4507-4511.
66. Grillot, D.A., R. Merino, J.C. Pena, W.C. Fanslow, F.D. Finkelman, C.B. Thompson, and G. Nunez. 1996. bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. J. Exp. Med. 2:381-391.
67. Young, F., E. Mizoguchi, A.K. Bhan, and F.W. Alt. 1997. Constitutive Bcl-2 expression during immunoglobulin heavy chain-promoted B cell differentiation expands novel precursor B cells. Immunity. 1:23-33.
68. Arakawa, H., T. Shimizu, and S. Takeda. 1996. Re-evaluation of the probabilities for productive rearrangements on the κ and λ loci. Int. Immunol. 1:91-99.
69. Nadel, B., P.A. Cazenave, and P. Sanchez. 1990. Murine lambda gene rearrangements: the stochastic model prevails over the ordered model. EMBO (Eur. Mol. Biol. Organ.) J. 2: 435-440.
70. Langman, R.E., and M. Cohn. 1995. The proportion of B-cell subsets expressing kappa and lambda light chains changes following antigenic selection. Immunol. Today. 3:141-144.
71. Rolink, A., U. Grawunder, D. Haasner, A. Strasser, and F. Melchers. 1993. Immature surface Ig+ B cells can continue to rearrange kappa and lambda L chain gene loci. J. Exp. Med. 4:1263-1270.