Cutting edge: expansion and activation of a population of autoreactive marginal zone B cells in a model of estrogen-induced lupus.
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.
Grimaldi
C M
CM
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Michael
D J
DJ
Diamond
B
B
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D000974:Antibodies, Antinuclear; D004958:Estradiol; D004247:DNA