Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation.
IL-4
affinity maturation
follicular dendritic cells
germinal center
memory B cells
scRNA-seq
scVDJ-seq
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
12 10 2021
12 10 2021
Historique:
received:
19
04
2020
revised:
02
06
2021
accepted:
27
08
2021
pubmed:
24
9
2021
medline:
10
11
2021
entrez:
23
9
2021
Statut:
ppublish
Résumé
B cells within germinal centers (GCs) enter cycles of antibody affinity maturation or exit the GC as memory cells or plasma cells. Here, we examined the contribution of interleukin (IL)-4 on B cell fate decisions in the GC. Single-cell RNA-sequencing identified a subset of light zone GC B cells expressing high IL-4 receptor-a (IL4Ra) and CD23 and lacking a Myc-associated signature. These cells could differentiate into pre-memory cells. B cell-specific deletion of IL4Ra or STAT6 favored the pre-memory cell trajectory, and provision of exogenous IL-4 in a wild-type context reduced pre-memory cell frequencies. IL-4 acted during antigen-specific interactions but also influenced bystander cells. Deletion of IL4Ra from follicular dendritic cells (FDCs) increased the availability of IL-4 in the GC, impaired the selection of affinity-matured B cells, and reduced memory cell generation. We propose that GC FDCs establish a niche that limits bystander IL-4 activity, focusing IL-4 action on B cells undergoing selection and enhancing memory cell differentiation.
Identifiants
pubmed: 34555336
pii: S1074-7613(21)00362-9
doi: 10.1016/j.immuni.2021.08.028
pmc: PMC8516727
mid: NIHMS1743371
pii:
doi:
Substances chimiques
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2256-2272.e6Subventions
Organisme : NIAID NIH HHS
ID : R01 AI045073
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007334
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.G.C. is an Scientific Advisory Board member of Be Biopharma and MiroBio.
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