Cutting Edge: Hormonal milieu, not antigenic specificity, determines the mature phenotype of autoreactive B cells.
Although both marginal zone and follicular B cells produce anti-DNA Abs in murine models of systemic lupus erythematosus, it has been unclear whether these distinct B cell subsets make identical or different Abs. Single-cell analysis demonstrates that the same DNA-reactive B cells can mature to either subset, depending on the hormonal environment. Anti-DNA B cells in estradiol-treated mice become marginal zone cells while identical cells from prolactin-treated mice become follicular cells. The B cell receptor signaling pathway is influenced by hormonal milieu. Thus, hormonal milieu and perhaps B cell receptor signaling, but not antigenic specificity, correlates with the differentiation pathway. These observations have implications for the pathogenesis and treatment of autoimmune disease.
Venkatesh
Jeganathan
J
Department of Medicine. Columbia University, New York, NY 10032, USA.
Peeva
Elena
E
Xu
Xiaonan
X
Diamond
Betty
B
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011388:Prolactin / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D000974:Antibodies, Antinuclear; D000941:Antigens; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell; D004958:Estradiol; D011388:Prolactin; D002118:Calcium