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...

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Veröffentlicht in:eLife 2023-07, Vol.12
Hauptverfasser: Ascani, Angelo, Torstensson, Sara, Risal, Sanjiv, Lu, Haojiang, Eriksson, Gustaw, Li, Congru, Teschl, Sabrina, Menezes, Joana, Sandor, Katalin, Ohlsson, Claes, Svensson, Camilla I, Karlsson, Mikael C I, Stradner, Martin Helmut, Obermayer-Pietsch, Barbara, Stener-Victorin, Elisabet
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Sprache:eng
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Zusammenfassung: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.86454