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 knockout 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.

Automated summary

This study found that variations in B cell numbers are associated with polycystic ovary syndrome (PCOS), but B cells are not central mediators of PCOS pathology. Hyperandrogenic women with PCOS have increased frequencies of specific types of B cells and higher levels of circulating immunoglobulin M (IgM), but transferring their serum to mice only leads to weight gain. Further experiments demonstrated that co-treatment with an androgen receptor antagonist can prevent PCOS-like phenotypes and alterations of B cell frequencies induced by dihydrotestosterone (DHT) in wild-type mice. B cell-deficient mice exposed to DHT still develop PCOS-like phenotypes.