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Science 31 March 2000:
Vol. 287. no. 5462, pp. 2501 - 2503
DOI: 10.1126/science.287.5462.2501
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Reports

T Cell-Independent Rescue of B Lymphocytes from Peripheral Immune Tolerance

Valerie Kouskoff, 1* Georges Lacaud, 2* David Nemazee 3dagger

Autoimmunity arises when immune tolerance to specific self-antigens is broken. The mechanisms leading to such a failure remain poorly understood. One hypothesis proposes that infectious agents or antigens can break B or T lymphocyte self-tolerance by expressing epitopes that mimic self. Using a transgenic immunoglobulin model, we show that challenge with self-mimicking foreign antigen rescues B cells from peripheral tolerance independent of T cell help, resulting in the accumulation of self-reactive cells in the lymph nodes and secretion of immunoglobulins that bind to a liver-expressed self-antigen. Therefore, our studies reveal a potentially important mechanism by which B lymphocytes can escape self-tolerance.

1 Department of Pediatrics,
2 Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
3 Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
*   Present address: Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1496, New York, NY 10029, USA.

dagger    To whom correspondence should be addressed. E-mail: nemazee{at}scripps.edu

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Visualization of the Genesis and Fate of Isotype-switched B Cells during a Primary Immune Response.
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