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- W3172247952 abstract "Abstract The random V(D)J recombination of immunoglobulins (Ig) loci often creates autoreactive B cell progenitors expressing self-recognized B-cell receptors (BCRs) 1 , which are eliminated or inactivated through an autoantigen-dependent central tolerance checkpoint to prevent autoimmune reactions 2,3 , a process thought to be restricted to the bone marrow (BM) in the adult mammals 4 . Here we report that early developing B cells are also present in the meninges of mice at all ages. Single cell RNA-sequencing (scRNA-seq) analysis revealed a consecutive trajectory of meningeal developing B cells in mice and non-human primates (NHPs). Parabiosis together with lineage tracing of hematopoietic stem cells (HSCs) showed that meningeal developing B cells are continuously replenished from the HSC-derived progenitors via a circulationindependent route. Importantly, autoreactive immature B cells which recognize myelin oligodendrocyte glycoprotein (MOG) 5 , a central nervous system (CNS)-specific antigen, are eliminated from the meninges but not BM. Furthermore, genetic deletion of MOG restored the self-reactive B cells in the meninges. Thus, we propose that meninges function as a unique reservoir for B cell development, allowing in situ negative selection of CNS-antigen-autoreactive B cells to ensure a local non-self-reactive immune repertoire." @default.
- W3172247952 created "2021-06-22" @default.
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- W3172247952 date "2021-06-03" @default.
- W3172247952 modified "2023-10-18" @default.
- W3172247952 title "CNS antigen-specific control of early B-lineage development in the meninges" @default.
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- W3172247952 doi "https://doi.org/10.1101/2021.06.03.446985" @default.
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