Estrogen increases the number of plasma cells and enhances their autoantibody production in nonautoimmune C57BL/6 mice.
The immunological consequences of chronic estrogen exposure in normal individuals are not known, particularly in relation to B cells. In this study, by employing ELIspot, image cytometry, flow cytometry, cytology, and ELISA, we show that long-term exposure of normal mice to estrogen activates B cells to produce higher numbers of not only immunoglobulin-producing cells, but also autoantibody-producing cells. Estrogen promoted a decrease in B220(+) splenic lymphocytes, but resulted in a 10-fold increase in plasma cells. Further, the output of immunoglobulins including autoantibodies from individual plasma cells from estrogen-exposed mice was markedly increased, suggesting B cell hyperactivity. Importantly, our findings show that treatment of normal mice, solely with estrogen, can override B cell tolerance and promote autoreactive B cells in normal individuals.
Verthelyi
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Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia, 24061, USA. Verthelyi@a1.cber.fda.gov
Ahmed
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D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000187:drug effects
D001323:Autoantibodies; D004967:Estrogens; D007074:Immunoglobulin G; D007075:Immunoglobulin M