Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges.
Immunity
; 54(12): 2784-2794.e6, 2021 12 14.
Article
em En
| MEDLINE
| ID: mdl-34626548
ABSTRACT
Self-reactive B cell progenitors are eliminated through central tolerance checkpoints, a process thought to be restricted to the bone marrow in mammals. Here, we identified a consecutive trajectory of B cell development in the meninges of mice and non-human primates. The meningeal B cells were located predominantly at the dural sinuses, where endothelial cells expressed essential niche factors to support B cell development. Parabiosis experiments together with lineage tracing showed that meningeal developing B cells were replenished continuously from hematopoietic stem cell (HSC)-derived progenitors via a circulation-independent route. Autoreactive immature B cells that recognized myelin oligodendrocyte glycoprotein (MOG), a central nervous system-specific antigen, were eliminated specifically from the meninges. Furthermore, genetic deletion of the Mog gene restored the self-reactive B cell population in the meninges. These findings identify the meninges as a distinct reservoir for B cell development, allowing in situ negative selection to ensure a locally non-self-reactive immune repertoire.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
/
Células Dendríticas
/
Células-Tronco Hematopoéticas
/
Indolamina-Pirrol 2,3,-Dioxigenase
/
Meninges
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article