The role of B cells in immune cell activation in polycystic ovary syndrome
- Medical University of Graz, Austria
- Karolinska Institute, Sweden
- University of Gothenburg, Sweden
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 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file and raw data can be found at Mendeley Data: doi:10.17632/tcc2mbmys4.1.
Article and author information
Author details
Barbara Obermayer-Pietsch
Elisabet Stener-Victorin
Funding
Vetenskapsrådet (2018-02435 and 2022-00550)
- Elisabet Stener-Victorin
Novo Nordisk Fonden (NNF22OC0072904 and NNF19OC0056647)
- Elisabet Stener-Victorin
Diabetes Fonden (DIA2021-633 and DIA2022-708)
- Elisabet Stener-Victorin
EMBO Scientific Exchange Grants 2021 (STF 8938)
- Angelo Ascani
European Research Council under the European Union's Horizon 2020 research and innovation program (866075)
- Camilla I Svensson
Knut and Alice Wallenberg Foundation (018.0161)
- Camilla I Svensson
Austrian Science Fund (W1241)
- Barbara Obermayer-Pietsch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Larisa V. Suturina, Scientific Center for Family Health and Human Reproduction problems, Russian Federation
Ethics
Animal experimentation: All animal experiments were approved by the Stockholm Ethical Committee for animal research (20485-2020) in accordance with the Swedish Board of Agriculture's regulations and recommendations (SJVFS 2019:9) and controlled by Comparative Medicine Biomedicum at the Karolinska Institutet in Stockholm, Sweden.
Human subjects: Participants provided oral and written informed consent after a positive vote of the Ethics committee of the Medical University Graz (EK 31-560 ex 18/19). The work here described has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans.
Version history
- Preprint posted: January 27, 2023 (view preprint)
- Received: January 27, 2023
- Accepted: June 16, 2023
- Accepted Manuscript published: July 4, 2023 (version 1)
- Version of Record published: July 20, 2023 (version 2)
Copyright
© 2023, Ascani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The role of B cells in immune cell activation in polycystic ovary syndrome
eLife 12:e86454.
https://doi.org/10.7554/eLife.86454
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