| First Author | Wang Y | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 12 | Pages | 2784-2794.e6 |
| PubMed ID | 34626548 | Mgi Jnum | J:318010 |
| Mgi Id | MGI:6856555 | Doi | 10.1016/j.immuni.2021.09.016 |
| Citation | Wang Y, et al. (2021) Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges. Immunity 54(12):2784-2794.e6 |
| abstractText | 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. |
