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J Immunol. 2001 Aug 15;167(4):1886-90.

Cutting edge: expansion and activation of a population of autoreactive marginal zone B cells in a model of estrogen-induced lupus.

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Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.


We have demonstrated previously that 17 beta-estradiol (E2) treatment of BALB/c mice transgenic for the heavy chain of a pathogenic anti-DNA Ab induces a lupus-like phenotype with expansion of anti-DNA B cells, elevation of anti-DNA Ab titers, and glomerular immunoglobulin deposition. To understand this loss of B cell tolerance, the effects of E2 on B cell development and activation were examined. A sustained increase in E2 resulted in an altered distribution of B cell subsets, with a diminished transitional population and an increase in marginal zone B cells. Depletion of CD4+ T cells did not abrogate these effects. Furthermore, the B cells that spontaneously secreted anti-DNA Abs displayed a marginal zone phenotype. Thus, a sustained increase in E2 alters B cell development, leading to the survival, expansion, and activation of a population of autoreactive marginal zone B cells implicating this B cell subset in autoimmunity.

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