B细胞激活因子
肾病
免疫学
免疫球蛋白A
免疫系统
生物
肾脏病理学
肾小球肾炎
抗体
B细胞
免疫球蛋白G
内分泌学
肾
糖尿病
作者
Douglas D. McCarthy,Julie Kujawa,C B Wilson,Adrian Papandile,Urjana Poreci,Elisa A. Porfilio,Lesley A. Ward,Melissa A. Lawson,Andrew J. Macpherson,Kathy D. McCoy,York Pei,Lea Novak,Jeannette Lee,Bruce A. Julian,Jan Novák,Ann Ranger,Jennifer L. Gommerman,Jeffrey L. Browning
摘要
B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria–reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.
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