Skip to main content
SpringerLink
Log in

Mechanism of antigen-driven selection in germinal centres

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

THE high affinity of antibodies produced during responses to T-cell-dependent antigens is associated with somatic mutation in the variable region of the immunoglobulin1–4. Indirect evidence indicates that: (1) this arises by a process of hypermutation, acting selectively on rearranged immunoglobulin variable-region genes, which is activated in centroblasts within germinal centres; and (2) centrocytes, the progeny of centroblasts, undergo selection on the basis of their ability to receive a positive signal from antigen5. We have now performed experiments analysing this selection process, and found that, on culture, centrocytes isolated from human tonsil kill themselves within a few hours by apoptosis6. This is not a feature of other tonsillar B cells. Centrocytes can be prevented from entering apoptosis if they are activated both through their receptors for antigen and a surface glycoprotein recognized by CD40 antibodies7,8.

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. Gearhart, P. J., Johnson, N. D., Douglas, R. & Hood, L. Nature 291, 29–34 (1981).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Bothwell, A. M. et al. Cell 24, 625–637 (1981).

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Griffiths, G. M., Berek, C., Kaartinen, M. & Milstein, C. Nature 312, 271–275 (1984).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. MacLennan, I. C. M. & Gray, D. Immunol. Rev. 91, 61–85 (1986).

    Article  CAS  PubMed  Google Scholar 

  6. Wyllie, A. H., Morris, R. G., Smith, A. L. & Dunlop, D. J. Path. 142, 67–77 (1982).

    Article  Google Scholar 

  7. Clark, E. A. & Ledbetter, J. A. Proc. natn. Acad. Sci. U.S.A. 83, 4494–4498 (1986).

    Article  ADS  CAS  Google Scholar 

  8. Ling, N. R., MacLennan, I. C. M. & Mason, D. Y. in Leucocyte Typing III (eds A. J. McMichael et al.) 302–335 (Oxford University Press, 1987).

    Google Scholar 

  9. Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181–184 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Tew, J. G. & Mandel, T. E. Immunology 37, 69–76 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Szakal, A. K., Kosco, M. H. & Tew, J. G. J. Immun. 140, 341–353 (1988).

    CAS  PubMed  Google Scholar 

  12. MacLennan, I. C. M., Gotch, F. M. & Golstein, P. Immunology 39, 109–117 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. MacLennan, I. C. M. & Golstein, P. J. Immun. 121, 2542–2546 (1978).

    CAS  PubMed  Google Scholar 

  14. Fliedner, T. M., Kesse, M., Cronkite, E. P. & Robertson, J. S. Ann. N.Y. Acad. Sci. 11, 578–594 (1964).

    ADS  Google Scholar 

  15. MacLennan, I. C. M., Liu, Y-J. & Ling, N. R. Curr. Topics Microbiol. Immunol. 141, 138–148 (1988).

    CAS  Google Scholar 

  16. Berek, C. & Milstein, S. Immunol. Rev. 96, 23–41 (1987).

    Article  CAS  PubMed  Google Scholar 

  17. Kraal, G., Hardy, R. R., Gallatin, W. M., Weissman, I. R. & Butcher, E. C. Eur. J. Immun. 16, 829–834 (1986).

    Article  CAS  Google Scholar 

  18. Klaus, G. G. B., Humphrey, J. H., Kunkle, A. & Dongworth, D. W. Immunol. Rev. 53, 3–28 (1980).

    Article  CAS  PubMed  Google Scholar 

  19. Coico, R. F., Bhogal, B. S. & Thorbecke, G. J. J. Immun. 131, 2254–2257 (1983).

    CAS  PubMed  Google Scholar 

  20. Tsujimoto, Y., Cossman, J., Jaffe, E. & Croce, C. M. Science 228, 1440–1443 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Graninger, W. B., Seto, M., Boutain, B., Goldman, P. & Korsemyre, S. J. J. clin. Invest. 80, 1512–1515 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vaux, D. L., Cory, S. & Adams, J. M. Nature 335, 440–442 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. McDonnell, T. J. et al. Cell 57, 79–88 (1989).

    Article  CAS  PubMed  Google Scholar 

  24. Walker, L. et al. Immunology 58, 533–589 (1986).

    Google Scholar 

  25. Ling, N. R., Bishop, S. & Jefferis, R. J. Immunol. Meth. 15, 279–289 (1979).

    Article  Google Scholar 

  26. Gill, P. G., Waller, X. A. & MacLennan, I. C. M. Immunology 33, 873–880 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lebacq-Verheyden, A. M. et al. Int. J. Cancer 32, 237–279 (1983).

    Article  Google Scholar 

  28. Van Camp, B., Thielmans, C. & Dehou, M. F. J. clin. Immun. 2, 67–74 (1982).

    Google Scholar 

  29. Kung, P. C., Goldstein, G., Reinhertz, E. L. & Schlossman, S. F. Science 206, 347–349 (1979).

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Partridge, L. J., Lowe, J., Hardie, D. L., Ling, N. R. & Jefferis, R. J. Immun. 128, 1–6 (1982).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TJ, UK

    Y-J. Liu, D. E. Joshua, J. Gordon & I. C. M. MacLennan

  2. Department of Anatomy, University of Birmingham Medical School, Birmingham, B15 2TJ, UK

    G. T. Williams & C. A. Smith

Authors
  1. Y-J. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. E. Joshua
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. T. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. A. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I. C. M. MacLennan
    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

Liu, YJ., Joshua, D., Williams, G. et al. Mechanism of antigen-driven selection in germinal centres. Nature 342, 929–931 (1989). https://doi.org/10.1038/342929a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/342929a0

  • Springer Nature Limited

This article is cited by

Search

Navigation