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

  1. Angelo Ascani

    Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Sara Torstensson

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4389-2662
  3. Sanjiv Risal

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Haojiang Lu

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Gustaw Eriksson

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0120-9028
  6. Congru Li

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Sabrina Teschl

    Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  8. Joana Menezes

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  9. Katalin Sandor

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3228-6907
  10. Claes Ohlsson

    Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  11. Camilla I Svensson

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  12. Mikael CI Karlsson

    Department of Microbiology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  13. Martin Helmut Stradner

    Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Competing interests
    The authors declare that no competing interests exist.
  14. Barbara Obermayer-Pietsch

    Department of Internal Medicine, Medical University of Graz, Graz, Austria
    For correspondence
    barbara.obermayer@medunigraz.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3543-1807
  15. Elisabet Stener-Victorin

    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
    For correspondence
    elisabet.stener-victorin@ki.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3424-1502

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

  1. 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

  1. Preprint posted: January 27, 2023 (view preprint)
  2. Received: January 27, 2023
  3. Accepted: June 16, 2023
  4. Accepted Manuscript published: July 4, 2023 (version 1)
  5. 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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  1. Angelo Ascani
  2. Sara Torstensson
  3. Sanjiv Risal
  4. Haojiang Lu
  5. Gustaw Eriksson
  6. Congru Li
  7. Sabrina Teschl
  8. Joana Menezes
  9. Katalin Sandor
  10. Claes Ohlsson
  11. Camilla I Svensson
  12. Mikael CI Karlsson
  13. Martin Helmut Stradner
  14. Barbara Obermayer-Pietsch
  15. Elisabet Stener-Victorin
(2023)
The role of B cells in immune cell activation in polycystic ovary syndrome
eLife 12:e86454.
https://doi.org/10.7554/eLife.86454

Share this article

https://doi.org/10.7554/eLife.86454

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