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
Burnet, F. M. The Clonal Selection Theory of Acquired immunity (Vanderbilt University Press, Nashville, 1959).
Kappler, J. W., Roehm, N. & Marrack, P. Cell 49, 273–280 (1987).
Kappler, J. W., Staerz, U., White, J. & Marrack, P. C. Nature 332, 35–40 (1988).
MacDonald, H. R. et al. Nature 332, 40–45 (1988).
Kisielow, P., Blüthmann, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–756 (1988).
Sha, W. C. et al. Nature 336, 73–76 (1988).
Nemazee, D. A. & Bürki, K. Nature 337, 562–566 (1989).
Nossal, G. J. V. A. Rev. Immun. 1, 33–62 (1983).
Goodnow, C. C. et al. Nature 334, 676–682 (1988).
Rammensee, H.-G., Kroschewski, R. & Frangoulis, B. Nature 339, 541–544 (1989).
Ramsdell, F., Lantz, T. & Fowlkes, B. J. Science 246, 1038–1041 (1989).
Burkly, L. C., Lo, D., Kanagawa, O., Brinster, R. L. & Flavell, R. A. Nature 342, 564–566 (1989).
Bonneville, M. et al. Nature 344, 163–165 (1990).
Blackman, M. A. et al. Nature 345, 540–542 (1990).
Schwartz, R. H. Science 248, 1349–1356 (1990).
Goodnow, C. C., Crosbie, J., Jorgensen, H., Brink, R. A. & Basten, A. Nature 342, 385–391 (1989).
Adams, E., Basten, A. & Goodnow, C. C. Proc. natn. Acad. Sci. U.S.A. 87, 5687–5691 (1990).
Naparstek, Y. et al. J. exp. Med. 164, 614–626 (1986).
Primi, D., Hammarstrom, L., Smith, C. I. E. & Moller, G. J. exp. Med. 145, 21–30 (1977).
Izui, S., Lambert, P. H., Fournie, G., Turler, H. & Miescher, P. A. J. exp. Med. 145, 1115 (1977).
Hang, L. et al. J. exp. Med. 157, 874–883 (1983).
Gleichmann, E. & Gleichmann, H. Eur. J. Immun. 6, 899–906 (1976).
Gleichmann, E., Van Elven, E. H. & Van der Veen, J. P. W. Eur. J. Immun. 12, 152–159 (1982).
Weigle, W. O. Adv. Immun. 30, 159–273 (1980).
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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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DOI: https://doi.org/10.1038/352532a0
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