Brg1 Supports B Cell Proliferation and Germinal Center Formation Through Enhancer Activation.
B cells
BAF
Brg1
SWI/SNF
antibody-formation
chromatin remodeling
enhancer activation
germinal center
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
06
05
2021
accepted:
11
08
2021
entrez:
20
9
2021
pubmed:
21
9
2021
medline:
21
12
2021
Statut:
epublish
Résumé
Activation and differentiation of B cells depend on extensive rewiring of gene expression networks through changes in chromatin structure and accessibility. The chromatin remodeling complex BAF with its catalytic subunit Brg1 was previously identified as an essential regulator of early B cell development, however, how Brg1 orchestrates gene expression during mature B cell activation is less clear. Here, we find that Brg1 is required for B cell proliferation and germinal center formation through selective interactions with enhancers. Brg1 recruitment to enhancers following B cell activation was associated with increased chromatin accessibility and transcriptional activation of their coupled promoters, thereby regulating the expression of cell cycle-associated genes. Accordingly, Brg1-deficient B cells were unable to mount germinal center reactions and support the formation of class-switched plasma cells. Our findings show that changes in B cell transcriptomes that support B cell proliferation and GC formation depend on enhancer activation by Brg1. Thus, the BAF complex plays a critical role during the onset of the humoral immune response.
Identifiants
pubmed: 34539636
doi: 10.3389/fimmu.2021.705848
pmc: PMC8440861
doi:
Substances chimiques
Nuclear Proteins
0
Transcription Factors
0
Smarca4 protein, mouse
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
705848Informations de copyright
Copyright © 2021 Schmiedel, Hezroni, Hamburg and Shulman.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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