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Central nervous system-compartmentalized pathogenic B cells promote neurological inflammation relapses

ABSTRACT: B cells have emerged as a critical player in autoimmune disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While locally educated B cells with a CNS non-self-reactive immune repertoire are observed at the brain borders, the specific function of these CNS-compartmentalized B cells in the neuroinflammation pathogenesis remains unclear. Here we demonstrated that autoreactive B cells promoted neuroinflammation through local cognate interaction with pathogenic T cells in the meninges. By selectively perturbing B cell compositions in the CNS through intra-cisterna magna injection, we found that CNS-compartmentalized autoreactive T-B interactions drove the influx of pro-inflammatory phagocytes and initiated vascular inflammation responses, which were dependent on the expression of class II major histocompatibility complex molecules. Selective targeting of B cells in the CNS effectively alleviated relapses of neurological inflammation. These findings elucidate the pathogenic functions of CNS-compartmentalized B cells, highlighting their potential as therapeutic targets for relapsing MS.

ORGANISM(S): Mus musculus

PROVIDER: GSE253740 | GEO | 2025/07/16

REPOSITORIES: GEO

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