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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
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    Cited by:

    1. Tatiana Erazo & Chiara M. Evans & Daniel Zakheim & Eren L. Chu & Alice Yunsi Refermat & Zahra Asgari & Xuejing Yang & Mariana Silva Ferreira & Sanjoy Mehta & Marco Vincenzo Russo & Andrea Knezevic & X, 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.

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