YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation.
B cells
CP: Immunology
YTHDF
antibodies
epigenetics
germinal center
m6A
mRNA
plasma cells
post-transcriptional
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
03 05 2022
03 05 2022
Historique:
received:
21
12
2021
revised:
25
02
2022
accepted:
12
04
2022
entrez:
4
5
2022
pubmed:
5
5
2022
medline:
7
5
2022
Statut:
ppublish
Résumé
Antibody-mediated immunity is initiated by B cell differentiation into multiple cell subsets, including plasmablast, memory, and germinal center (GC) cells. B cell differentiation trajectories are determined by transcription factors, yet very few mechanisms that specifically determine early B cell fates have been described. Here, we report a post-transcriptional mechanism that suppresses the plasmablast genetic program and promotes GC B cell fate commitment. Single-cell RNA-sequencing analysis reveals that antigen-specific B cell precursors at the pre-GC stage upregulate YTHDF2, which enhances the decay of methylated transcripts. Ythdf2-deficient B cells exhibit intact proliferation and activation, whereas differentiation into GC B cells is blocked. Mechanistically, B cells require YTHDF2 to attenuate the plasmablast genetic program during GC seeding, and transcripts of key plasmablast-regulating genes are methylated and bound by YTHDF2. Collectively, this study reveals how post-transcriptional suppression of gene expression directs appropriate B cell fate commitment during initiation of the adaptive immune response.
Identifiants
pubmed: 35508130
pii: S2211-1247(22)00542-3
doi: 10.1016/j.celrep.2022.110778
pmc: PMC9108551
pii:
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110778Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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