西湖大学何丹阳研究组发现了脑膜B细胞同源相互作用依赖性致病性驱动神经炎症复发。这一研究成果发表在2025年7月15日出版的国际学术期刊《免疫学》上。

小组证明了脑边界的自身反应性B细胞通过直接参与脑源性T细胞而加速神经炎症。在2D2转移实验性自身免疫性脑脊髓炎（EAE）模型中，大脑膜内注射以选择性操纵脑膜B细胞群为主题，揭示了轻脑膜中自身反应性B-T相互作用放大了局部促炎环，促进了中性粒细胞的募集和内皮细胞的激活。这一机制需要B细胞表达主要组织相容性复合体II类（MHC II类），T细胞产生粒细胞-巨噬细胞集落刺激因子（GM-CSF）。

此外，在被动EAE模型中，靶向清除脑定位B细胞可减轻EAE复发。这些发现证实了脑定位的自身反应性B细胞是神经炎症的关键启动物，也是复发性多发性硬化症的有希望的治疗靶点。

据介绍，B细胞是中枢神经系统（CNS）自身免疫性疾病（包括多发性硬化症（MS））的主要驱动因素。虽然脑膜通常维持严格的非自我反应性B细胞库，但这种局部免疫耐受的破坏如何导致病理尚不清楚。

附：英文原文

Title: Cognate interaction-dependent pathogenicity of meningeal B cells drives neuroinflammation relapse

Author: Yan Wang, Di Xu, Shaorui Liu, Haoyang Li, Yinsheng Wang, Hui Li, Heping Xu, Danyang He

Issue&Volume: 2025-07-15

Abstract: 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.

DOI: 10.1016/j.immuni.2025.06.016

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00285-7