PRMT5 is essential for B cell development and germinal center dynamics.
Animals
Apoptosis
/ immunology
B-Lymphocytes
/ immunology
Cell Differentiation
/ immunology
Cell Proliferation
/ physiology
Cells, Cultured
Disease Models, Animal
Female
Gene Knockdown Techniques
Germinal Center
/ cytology
Humans
Immunity, Humoral
/ physiology
Lymphocyte Activation
/ immunology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Primary Cell Culture
Protein-Arginine N-Methyltransferases
/ genetics
Signal Transduction
/ physiology
Trichostrongyloidea
/ immunology
Trichostrongyloidiasis
/ immunology
Tumor Suppressor Protein p53
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 01 2019
03 01 2019
Historique:
received:
22
06
2018
accepted:
04
12
2018
entrez:
4
1
2019
pubmed:
4
1
2019
medline:
21
3
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30604754
doi: 10.1038/s41467-018-07884-6
pii: 10.1038/s41467-018-07884-6
pmc: PMC6318318
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
Prmt5 protein, mouse
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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