title: Estrogen receptor alpha promotes lupus in (NZB×NZW)F1 mice in a B cell intrinsic manner.
abstract: Lupus is a systemic autoimmune disease characterized by the production of autoreactive antibodies against nuclear antigens. Women are disproportionately affected by lupus, and this sex bias is thought to be due, in large part, to the ability of estrogens to promote lupus pathogenesis. Previously, we have shown that global deletion of estrogen receptor alpha (ERα) significantly attenuated loss of tolerance, immune cell activation, autoantibody production, and the development of lupus nephritis. Here we show that targeted deletion of ERα specifically in B cells retards production of pathogenic autoantibodies and the development of nephritis in lupus-prone (NZB×NZW)F1 mice. Furthermore, we observed that ERα deletion in B cells was associated with decreased B cell activation in young, pre-autoimmune (NZB×NZW)F1 females. Altogether, these data suggest that ERα acts in a B cell-intrinsic manner to control B cell activation, autoantibody production, and lupus nephritis.
authors.affiliation: Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Tabor
authors.affiliation: Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: kagould@unmc.edu.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gould
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D018941:Antigens, CD19 / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D019426:Integrases / Q000235:genetics; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology*; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB
chemical_list: D000974:Antibodies, Antinuclear; D018941:Antigens, CD19; C000604812:CD19 antigen, mouse; D047628:Estrogen Receptor alpha; D007074:Immunoglobulin G; C045073:Cre recombinase; D019426:Integrases
keywords: B cell; Estrogen receptor alpha; Immune cell activation; Immunologic tolerance; Lupus