Skip to main content
SpringerLink
Log in

Antigen-induced B-cell death and elimination during germinal-centre immune responses

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

DURING an immune response, hypermutation of immunoglobulin genes in B cells proliferating within germinal centres (GCs) generates variant antibodies that react with higher affinity against either foreign or self antigens1-9. Several experiments suggest that self-reactive B cells may be censored at this stage of the immune response10-12, but the rarity of these cells and the dynamic nature of GC reactions have prevented direct analysis. We have developed a new approach to visualize the fate of antigen-specific B cells during GC reactions by seeding an ongoing immune response with lysozyme-specific B cells from immunoglobulin-gene transgenic animals. Administration of soluble antigen at the peak of the GC response rapidly eliminates lysozyme-specific GC B cells in two waves of apoptosis, one within the GC and a second in cells that have redistributed to lymphoid zones that are rich in T cells. Elimination of these cells is inhibited by constitutive expression of the follicular lymphoma proto-oncogene bcl-2. These findings reveal censoring steps that may normally prevent affinity maturation of autoantibodies to systemic autoantigens, and might be used by pathogenic microorganisms or in clinical strategies to interfere with antibody responses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Weigert, M. G., Cesari, I. M., Yonkovich, S. J. & Cohn, M. Nature 228, 1045–1047 (1970).

    Article  ADS  CAS  Google Scholar 

  2. Tonegawa, S. Nature 302, 575–581 (1983).

    Article  ADS  CAS  Google Scholar 

  3. Kocks, C. & Rajewsky, K. A. Rev. Immun. 7, 537–559 (1989).

    Article  CAS  Google Scholar 

  4. Jacob, J., Kelsoe, G., Rajewsky, K. & Weiss, U. Nature 354, 389–392 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Berek, C. Berger, A. & Apel, M. Cell 67, 1121–1129 (1991).

    Article  CAS  Google Scholar 

  6. Diamond, B. & Scharff, M. Proc. natn. Acad. Sci. U.S.A. 81, 5841–5844 (1984).

    Article  ADS  CAS  Google Scholar 

  7. Shlomchik, M. J., Marshak-Rothstein, A., Wolfowicz, C. B., Rothstein, T. L. & Weigert, M. G. Nature 328, 805–811 (1987).

    Article  ADS  CAS  Google Scholar 

  8. Shlomchik, M. et al. J. exp. Med. 171, 265–292 (1990).

    Article  CAS  Google Scholar 

  9. Diamond, B. et al. A. Rev. Immun. 10, 731–757 (1992).

    Article  CAS  Google Scholar 

  10. Linton, P.-J., Rudie, A. & Klinman, N. R. J. Immun. 146, 4099–4104 (1991).

    CAS  Google Scholar 

  11. Dintzis, H. M. & Dintzis, R. Z. Proc. natn. Acad. Sci. USA. 89, 1113–1117 (1992).

    Article  ADS  CAS  Google Scholar 

  12. Nossal, G. J. V., Karvelas, M. & Pulendran, B. Proc. natn. Acad. Sci. U.S.A. 90, 3088–3092 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Goodnow, C. C. et al. Nature 334, 676–682 (1988).

    Article  ADS  CAS  Google Scholar 

  14. Gammon, G. et al. Immunol. Rev. 98, 53–73 (1987).

    Article  CAS  Google Scholar 

  15. Lavoie, T. B., Drohan, W. N. & Smith-Gill, S. J. J. Immun. 148, 503–513 (1992).

    CAS  PubMed  Google Scholar 

  16. Liu, Y.-J., Zhang, J., Lane, P. J. L., Chan, E. Y.-T. & MacLennan, I. C. M. Eur. J. Immun. 21, 2951–2962 (1991).

    Article  CAS  Google Scholar 

  17. Strasser, A. et al. Proc. natn. Acad. Sci. U.S.A. 88, 8661–8665 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell Biol. 119, 493–501 (1992).

    Article  CAS  Google Scholar 

  19. Liu, Y.-J. et al. Nature 342, 929–931 (1989).

    Article  ADS  CAS  Google Scholar 

  20. MacLennan, I. C. M. A. Rev. Immun. 12, 117–139 (1994).

    Article  CAS  Google Scholar 

  21. Gray, D., Dullforce, P. & Jainandusing, S. J. exp. Med. 180, 141–155 (1994).

    Article  CAS  Google Scholar 

  22. Pulendran, B., Kannaroukis, G., Nouri, S., Smith, K. G. C. & Nossal, G. J. V. Nature 375, 331–334 (1995).

    Article  ADS  CAS  Google Scholar 

  23. Cyster, J., Hartley, S. & Goodnow, C. C. Nature 371, 389–395 (1994).

    Article  ADS  CAS  Google Scholar 

  24. Radic, M. Z. & Weigert, M. A. Rev. Immun. 12, 487–520 (1994).

    Article  CAS  Google Scholar 

  25. Kemp, D. J., Coppel, R. L. & Anders, R. F. A. Rev. Microbiol. 41, 181–208 (1987).

    Article  CAS  Google Scholar 

  26. Padlan, E. A. et al. Proc. natn. Acad. Sci. U.S.A. 86, 5938–5942 (1989).

    Article  ADS  CAS  Google Scholar 

  27. Prager, E. M. & Wilson, A. C. J. biol. Chem. 246, 523–530 (1971).

    CAS  PubMed  Google Scholar 

  28. Cooke, M. P. et al. J. exp. Med. 179, 425–438 (1994).

    Article  CAS  Google Scholar 

  29. Lagasse, E. & Weissman, I. L. Blood 79, 1907–1915 (1992).

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Kevan M. Shokat

    Present address: Departments of Chemistry and Molecular Biology, Princeton University, Princeton, New Jersey, 08544, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Microbiology and Immunology, Beckman Center, Stanford University School of Medicine, Stanford, California, 94305, USA

    Kevan M. Shokat & Christopher C. Goodnow

Authors
  1. Kevan M. Shokat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher C. Goodnow
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shokat, K., Goodnow, C. Antigen-induced B-cell death and elimination during germinal-centre immune responses. Nature 375, 334–338 (1995). https://doi.org/10.1038/375334a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/375334a0

  • Springer Nature Limited

This article is cited by

Search

Navigation