PRMT5 is essential for B cell development and germinal center dynamics

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. King, Claudia L. Kleinman, Stéphane Richard and Javier M. Di Noia ()
Additional contact information
Ludivine C. Litzler: Institut de Recherches Cliniques de Montréal
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
Stephen P. Methot: Institut de Recherches Cliniques de Montréal
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
Irah L. King: McGill University Health Centre
Claudia L. Kleinman: Segal Cancer Center, Lady Davis Institute for Medical Research
Stéphane Richard: Segal Cancer Center, Lady Davis Institute for Medical Research
Javier M. Di Noia: Institut de Recherches Cliniques de Montréal

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-07884-6

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