| First Author | Wang Y | Year | 2025 |
| Journal | Immunity | Volume | 58 |
| Issue | 9 | Pages | 2256-2270.e8 |
| PubMed ID | 40669468 | Mgi Jnum | J:372057 |
| Mgi Id | MGI:8244561 | Doi | 10.1016/j.immuni.2025.06.016 |
| Citation | Wang Y, et al. (2025) Cognate interaction-dependent pathogenicity of meningeal B cells drives neuroinflammation relapse. Immunity 58(9):2256-2270.e8 |
| abstractText | B cells are central drivers of central nervous system (CNS) autoimmune disorders, including multiple sclerosis (MS). Although the brain meninges normally maintain a stringently non-self-reactive B cell repertoire, how disruption of this local immune tolerance contributes to pathology remains unclear. Here, we demonstrated that autoreactive B cells at the brain border accelerated neuroinflammation by directly engaging encephalitogenic T cells. Intracisterna magna injections, used to selectively manipulate meningeal B cell populations in the 2D2 transfer experimental autoimmune encephalomyelitis (EAE) model, revealed that autoreactive B-T interactions in the leptomeninges amplified a local pro-inflammatory loop, promoting neutrophil recruitment and endothelial activation before disease onset. This mechanism required major histocompatibility complex class II (MHC class II) expression by B cells and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by T cells. Furthermore, targeted depletion of brain-localized B cells attenuated EAE relapses in a passive EAE model. These findings establish brain-localized autoreactive B cells as crucial initiators of neuroinflammation and promising therapeutic targets in relapsing MS. |
