The role of B cells in immune cell activation in polycystic ovary syndrome
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Curated by eLife
eLife assessment
This manuscript provides important findings and would be of interest to specialists and researchers dealing with polycystic ovarian syndrome. Based on the compelling evidence, the authors present significant results on the role of B cells in immune cell activation in PCOS. However, there are some remarks regarding the statistics and data presentation.
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- Immunology and Inflammation (eLife)
Abstract
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.
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eLife assessment
This manuscript provides important findings and would be of interest to specialists and researchers dealing with polycystic ovarian syndrome. Based on the compelling evidence, the authors present significant results on the role of B cells in immune cell activation in PCOS. However, there are some remarks regarding the statistics and data presentation.
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Reviewer #1 (Public Review):
In this manuscript, the authors have demonstrated the direct effect of androgen receptor activation on B - cell frequencies. In the clinical part of the research, they have found increased frequencies of age-associated double-negative B memory cells and elevated levels of circulating immunoglobulin M (IgM) in women with hyperandrogenic phenotypes of PCOS. The major study strengths are driven by their experimental part. It was shown that the transfer of serum IgG from women with PCOS into wild-type female mice increases body weight, whereas RAG1 knock-out mice, which lack mature T- and B cells, do not demonstrate any signs of hyperandrogenism. Simultaneously, an androgen receptor antagonist prevents increased B cell numbers induced by androgens, whereas B cell-deficient mice are not protected from developing …
Reviewer #1 (Public Review):
In this manuscript, the authors have demonstrated the direct effect of androgen receptor activation on B - cell frequencies. In the clinical part of the research, they have found increased frequencies of age-associated double-negative B memory cells and elevated levels of circulating immunoglobulin M (IgM) in women with hyperandrogenic phenotypes of PCOS. The major study strengths are driven by their experimental part. It was shown that the transfer of serum IgG from women with PCOS into wild-type female mice increases body weight, whereas RAG1 knock-out mice, which lack mature T- and B cells, do not demonstrate any signs of hyperandrogenism. Simultaneously, an androgen receptor antagonist prevents increased B cell numbers induced by androgens, whereas B cell-deficient mice are not protected from developing a PCOS-like phenotype when exposed to DHT. Generally, the author's conclusions are based on evidence, and this study opens up a new direction of research in this area.
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Reviewer #2 (Public Review):
The significance of these findings is that the role of B cells in mediating cardiometabolic complications in PCOS is not completely understood. The approach taken by this research group is both innovative and translational. One of the clear strengths of this manuscript is that it combines basic research with clinical studies in PCOS women.
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