The role of B cells in immune cell activation in polycystic ovary syndrome

Variations in B cell numbers are associated with polycystic ovary syndrome (PCOS) through unknown mechanisms. Here we demonstrate that B cells are not central mediators of PCOS pathology and that their frequencies are altered as a direct effect of androgen receptor activation. Hyperandrogenic women with PCOS have increased frequencies of age-associated double-negative B memory cells and increased levels of circulating immunoglobulin M (IgM). However, the transfer of serum IgG from women into wild-type female mice induces only an increase in body weight. Furthermore, RAG1 knock-out mice, which lack mature T- and B cells, fail to develop any PCOS-like phenotype. In wild-type mice, co-treatment with flutamide, an androgen receptor antagonist, prevents not only the development of a PCOS-like phenotype but also alterations of B cell frequencies induced by dihydrotestosterone (DHT). Finally, B cell-deficient mice, when exposed to DHT, are not protected from developing a PCOS-like phenotype. These results urge further studies on B cell functions and their effects on autoimmune comorbidities highly prevalent among women with PCOS.B细胞数量的变异与多囊卵巢综合征（polycystic ovary syndrome, PCOS）存在关联，但其背后的调控机制尚不明确。本研究证实，B细胞并非多囊卵巢综合征病理进程的核心介导因子，其频率变化是雄激素受体激活的直接效应。罹患多囊卵巢综合征的高雄激素血症女性，其年龄相关性双阴性记忆B细胞的比例升高，循环免疫球蛋白M（immunoglobulin M, IgM）水平也有所上升。然而，将女性血清免疫球蛋白G（IgG）移植至野生型雌性小鼠体内，仅会引发小鼠体重增加。此外，缺乏成熟T细胞和B细胞的RAG1敲除小鼠，不会出现任何多囊卵巢综合征样表型。在野生型小鼠中，联合使用雄激素受体拮抗剂氟他胺（flutamide），不仅可阻断多囊卵巢综合征样表型的发生，还能改善二氢睾酮（dihydrotestosterone, DHT）诱导的B细胞频率异常。最终，暴露于二氢睾酮的B细胞缺陷小鼠，并未表现出对多囊卵巢综合征样表型的抵抗能力。上述结果表明，亟需针对B细胞的功能及其与多囊卵巢综合征女性高发的自身免疫合并症之间的关联开展进一步研究。