Single cell clonal analysis identifies an AID-dependent pathway of plasma cell differentiation.
activation-induced deaminase
germinal center
plasma cell
single cell sequencing
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 12 2022
06 12 2022
Historique:
revised:
13
09
2022
received:
08
03
2022
accepted:
15
09
2022
pubmed:
8
10
2022
medline:
15
12
2022
entrez:
7
10
2022
Statut:
ppublish
Résumé
Germinal centers (GC) are microstructures where B cells that have been activated by antigen can improve the affinity of their B cell receptors and differentiate into memory B cells (MBCs) or antibody-secreting plasma cells. Here, we have addressed the role of activation-induced deaminase (AID), which initiates somatic hypermutation and class switch recombination, in the terminal differentiation of GC B cells. By combining single cell transcriptome and immunoglobulin clonal analysis in a mouse model that traces AID-experienced cells, we have identified a novel subset of late-prePB cells (L-prePB), which shares the strongest clonal relationships with plasmablasts (PBs). Mice lacking AID have various alterations in the size and expression profiles of transcriptional clusters. We find that AID deficiency leads to a reduced proportion of L-prePB cells and severely impairs transitions between the L-prePB and the PB subsets. Thus, AID shapes the differentiation fate of GC B cells by enabling PB generation from a prePB state.
Identifiants
pubmed: 36205653
doi: 10.15252/embr.202255000
pmc: PMC9724673
doi:
Banques de données
GEO
['GSE189775']
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55000Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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