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Cutting Edge |
Departments of
*
Microbiology and Immunology and
Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
We have demonstrated previously that 17 
-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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