CNS antigen-specific control of early B-lineage development in the meninges

• DOI: 10.1101/2021.06.03.446985
• Publication Date: 2021-06-04T03:51:05Z
• Authors: Yan Wang; Dianyu Chen; Di Xu; Chao Huang; Danyang He; Heping Xu
• Keywords: Meninges

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 be restricted the bone marrow (BM) in adult mammals 4 . Here we report that early developing cells also present meninges mice at all ages. Single RNA-sequencing (scRNA-seq) analysis revealed consecutive trajectory meningeal and non-human primates (NHPs). Parabiosis together with lineage tracing hematopoietic stem (HSCs) showed continuously replenished from HSC-derived via circulationindependent route. Importantly, immature recognize myelin oligodendrocyte glycoprotein (MOG) 5 nervous system (CNS)-specific antigen, but not BM. Furthermore, genetic deletion MOG restored self-reactive meninges. Thus, propose function as unique reservoir for development, allowing situ negative selection CNS-antigen-autoreactive ensure local non-self-reactive immune repertoire.