Peripheral apoptosis and limited clonal deletion during physiologic murine B lymphocyte development.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 Jun 2024
01 Jun 2024
Historique:
received:
06
12
2023
accepted:
21
05
2024
medline:
2
6
2024
pubmed:
2
6
2024
entrez:
1
6
2024
Statut:
epublish
Résumé
Self-reactive and polyreactive B cells generated during B cell development are silenced by either apoptosis, clonal deletion, receptor editing or anergy to avoid autoimmunity. The specific contribution of apoptosis to normal B cell development and self-tolerance is incompletely understood. Here, we quantify self-reactivity, polyreactivity and apoptosis during physiologic B lymphocyte development. Self-reactivity and polyreactivity are most abundant in early immature B cells and diminish significantly during maturation within the bone marrow. Minimal apoptosis still occurs at this site, however B cell receptors cloned from apoptotic B cells show comparable self-reactivity to that of viable cells. Apoptosis increases dramatically only following immature B cells leaving the bone marrow sinusoids, but above 90% of cloned apoptotic transitional B cells are not self-reactive/polyreactive. Our data suggests that an apoptosis-independent mechanism, such as receptor editing, removes most self-reactive B cells in the bone marrow. Mechanistically, lack of survival signaling rather than clonal deletion appears to be the underpinning cause of apoptosis in most transitional B cells in the periphery.
Identifiants
pubmed: 38824171
doi: 10.1038/s41467-024-49062-x
pii: 10.1038/s41467-024-49062-x
doi:
Substances chimiques
Receptors, Antigen, B-Cell
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4691Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011975
Pays : United States
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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