17 beta-estradiol, but not 5 alpha-dihydrotestosterone, augments antibodies to double-stranded deoxyribonucleic acid in nonautoimmune C57BL/6J mice.
The influence of sex hormones on the immune response to foreign antigens as well as self-antigens is now recognized. In this study, we investigated the influence of gender and sex hormones on the development of antibodies to double-stranded DNA in nonautoimmune C57BL/6J mice. Immunoglobulin G (IgG) anti-dsDNA antibodies are commonly present in lupus patients and several autoimmune disease-prone murine strains. We found that C57BL/6J mice have detectable antibodies (IgM and IgG, but not IgA) to dsDNA. Interestingly, the incidence and level of IgG anti-dsDNA antibodies were lower in male than in female mice. Orchidectomy or administration of 5 alpha-dihydrotestosterone to orchidectomized male mice had minimal effects on these antibodies. In contrast, administration of 17 beta-estradiol to orchidectomized or intact males significantly increased both the incidence and levels of anti-dsDNA antibodies. In female mice, ovariectomy decreased whereas administration of estrogen augmented the incidence and levels of anti-dsDNA antibodies in ovariectomized as well as intact female mice. Kinetic studies revealed that estrogen treatment of male and female mice induced earlier and sustained expression of IgG anti-dsDNA antibodies compared to controls. IgG subisotype analysis showed IgG2b to be predominant. In summary, our findings suggest that estrogen, but not dihydrotestosterone, promotes anti-dsDNA antibodies in normal mice.
Verthelyi
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Department of Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Ahmed
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SA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D012016:Reference Values
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D013196:Dihydrotestosterone; D004958:Estradiol; D004247:DNA