IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-07884-6.html
   My bibliography  Save this article

PRMT5 is essential for B cell development and germinal center dynamics

Author

Listed:
  • Ludivine C. Litzler

    (Institut de Recherches Cliniques de Montréal
    Department of Biochemistry and molecular medicine)

  • Astrid Zahn

    (Institut de Recherches Cliniques de Montréal)

  • Alexandre P. Meli

    (McGill University Health Centre)

  • Steven Hébert

    (Segal Cancer Center, Lady Davis Institute for Medical Research)

  • Anne-Marie Patenaude

    (Institut de Recherches Cliniques de Montréal
    Genos)

  • Stephen P. Methot

    (Institut de Recherches Cliniques de Montréal
    Friedrich Miescher Institute for Biomedical Research)

  • Adrien Sprumont

    (Institut de Recherches Cliniques de Montréal)

  • Thérence Bois

    (Institut de Recherches Cliniques de Montréal)

  • Daisuke Kitamura

    (Tokyo University of Science, Noda)

  • Santiago Costantino

    (Research Center of the Hospital Maisonneuve-Rosemont
    Université de Montréal)

  • Irah L. King

    (McGill University Health Centre)

  • Claudia L. Kleinman

    (Segal Cancer Center, Lady Davis Institute for Medical Research
    McGill University)

  • Stéphane Richard

    (Segal Cancer Center, Lady Davis Institute for Medical Research
    McGill University)

  • Javier M. Di Noia

    (Institut de Recherches Cliniques de Montréal
    Department of Biochemistry and molecular medicine
    McGill University
    Université de Montréal)

Abstract

Mechanisms regulating B cell development, activation, education in the germinal center (GC) and differentiation, underpin the humoral immune response. Protein arginine methyltransferase 5 (Prmt5), which catalyzes most symmetric dimethyl arginine protein modifications, is overexpressed in B cell lymphomas but its function in normal B cells is poorly defined. Here we show that Prmt5 is necessary for antibody responses and has essential but distinct functions in all proliferative B cell stages in mice. Prmt5 is necessary for B cell development by preventing p53-dependent and p53-independent blocks in Pro-B and Pre-B cells, respectively. By contrast, Prmt5 protects, via p53-independent pathways, mature B cells from apoptosis during activation, promotes GC expansion, and counters plasma cell differentiation. Phenotypic and RNA-seq data indicate that Prmt5 regulates GC light zone B cell fate by regulating transcriptional programs, achieved in part by ensuring RNA splicing fidelity. Our results establish Prmt5 as an essential regulator of B cell biology.

Suggested Citation

  • Ludivine C. Litzler & Astrid Zahn & Alexandre P. Meli & Steven Hébert & Anne-Marie Patenaude & Stephen P. Methot & Adrien Sprumont & Thérence Bois & Daisuke Kitamura & Santiago Costantino & Irah L. Ki, 2019. "PRMT5 is essential for B cell development and germinal center dynamics," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07884-6
    DOI: 10.1038/s41467-018-07884-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07884-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-07884-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tatiana Erazo & Chiara M. Evans & Daniel Zakheim & Karen L. Chu & Alice Yunsi Refermat & Zahra Asgari & Xuejing Yang & Mariana Silva Ferreira & Sanjoy Mehta & Marco Vincenzo Russo & Andrea Knezevic & , 2022. "TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07884-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.