First Author | Litzler LC | Year | 2019 |
Journal | Nat Commun | Volume | 10 |
Issue | 1 | Pages | 22 |
PubMed ID | 30604754 | Mgi Jnum | J:271592 |
Mgi Id | MGI:6277833 | Doi | 10.1038/s41467-018-07884-6 |
Citation | Litzler LC, et al. (2019) PRMT5 is essential for B cell development and germinal center dynamics. Nat Commun 10(1):22 |
abstractText | 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. |