Breakdown of self-tolerance in anergic B lymphocytes

Abstract

PRODUCTION of autoantibodies, which characterizes most autoimmune diseases, is normally avoided by active elimination1–7 or functional inactivation (anergy) 8–15 of B and T lymphocytes bearing receptors for self antigens. The mechanisms leading to the escape of self-reactive clones from these normal tolerance mechanisms in autoimmune diseases nevertheless remain obscure. Here, we demonstrate that clonal anergy in B lymphocytes is a reversible process, and that silenced self-reactive B cells can be reactivated under particular conditions to give rise to vigorous antibody responses. Reactivation of anergic lymphocytes may explain many examples of transient autoimmune reactions in normal individuals, and may under pathological conditions be important in the development of chronic autoimmune disease.

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References

  1. 1

    Burnet, F. M. The Clonal Selection Theory of Acquired immunity (Vanderbilt University Press, Nashville, 1959).

    Google Scholar 

  2. 2

    Kappler, J. W., Roehm, N. & Marrack, P. Cell 49, 273–280 (1987).

    CAS  Article  Google Scholar 

  3. 3

    Kappler, J. W., Staerz, U., White, J. & Marrack, P. C. Nature 332, 35–40 (1988).

    ADS  CAS  Article  Google Scholar 

  4. 4

    MacDonald, H. R. et al. Nature 332, 40–45 (1988).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Kisielow, P., Blüthmann, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–756 (1988).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Sha, W. C. et al. Nature 336, 73–76 (1988).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Nemazee, D. A. & Bürki, K. Nature 337, 562–566 (1989).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Nossal, G. J. V. A. Rev. Immun. 1, 33–62 (1983).

    CAS  Article  Google Scholar 

  9. 9

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

    ADS  CAS  Article  Google Scholar 

  10. 10

    Rammensee, H.-G., Kroschewski, R. & Frangoulis, B. Nature 339, 541–544 (1989).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Ramsdell, F., Lantz, T. & Fowlkes, B. J. Science 246, 1038–1041 (1989).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Burkly, L. C., Lo, D., Kanagawa, O., Brinster, R. L. & Flavell, R. A. Nature 342, 564–566 (1989).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Bonneville, M. et al. Nature 344, 163–165 (1990).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Blackman, M. A. et al. Nature 345, 540–542 (1990).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Schwartz, R. H. Science 248, 1349–1356 (1990).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Goodnow, C. C., Crosbie, J., Jorgensen, H., Brink, R. A. & Basten, A. Nature 342, 385–391 (1989).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Adams, E., Basten, A. & Goodnow, C. C. Proc. natn. Acad. Sci. U.S.A. 87, 5687–5691 (1990).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Naparstek, Y. et al. J. exp. Med. 164, 614–626 (1986).

    CAS  Article  Google Scholar 

  19. 19

    Primi, D., Hammarstrom, L., Smith, C. I. E. & Moller, G. J. exp. Med. 145, 21–30 (1977).

    CAS  Article  Google Scholar 

  20. 20

    Izui, S., Lambert, P. H., Fournie, G., Turler, H. & Miescher, P. A. J. exp. Med. 145, 1115 (1977).

    CAS  Article  Google Scholar 

  21. 21

    Hang, L. et al. J. exp. Med. 157, 874–883 (1983).

    CAS  Article  Google Scholar 

  22. 22

    Gleichmann, E. & Gleichmann, H. Eur. J. Immun. 6, 899–906 (1976).

    Article  Google Scholar 

  23. 23

    Gleichmann, E., Van Elven, E. H. & Van der Veen, J. P. W. Eur. J. Immun. 12, 152–159 (1982).

    CAS  Article  Google Scholar 

  24. 24

    Weigle, W. O. Adv. Immun. 30, 159–273 (1980).

    CAS  Article  Google Scholar 

Download references

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Goodnow, C., Brink, R. & Adams, E. Breakdown of self-tolerance in anergic B lymphocytes. Nature 352, 532–536 (1991). https://doi.org/10.1038/352532a0

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