Multiple sclerosis is associated with lesions not just in the white matter, but also involving the cortex. Cortical involvement has been linked to greater disease severity and hence understanding the factor underlying cortical pathology could help identify new therapeutic strategies for multiple sclerosis. The critical role of B cells in multiple sclerosis has been clarified by multiple pivotal trials of B cell depletion in people with multiple sclerosis. The presence of B cell rich areas of meningeal inflammation in multiple sclerosis has been identified at all stages of multiple sclerosis. Leptomeningeal inflammation is associated with greater extent of cortical demyelination and neuronal loss and with greater disease severity. Recent studies have identified several potential mechanisms by which B cells may mediate cortical injury including antibody production, extracellular vesicles containing neurotoxic substances and production of pro-inflammatory cytokines. Additionally, B cells may indirectly mediate cortical damage through effects on T cells, macrophages or microglia. Several animal models replicate the meningeal inflammation and cortical injury noted in people with multiple sclerosis. Studies in these models have identified BTK inhibition and type II anti-CD20 antibodies as potential agents that can impact meningeal inflammation. Trials of anti-CD20 monoclonal antibodies in people with multiple sclerosis have unsuccessfully attempted to eliminate B cells in the leptomeninges. New strategies to target B cells in multiple sclerosis include BTK inhibition and cell-based therapies aimed at B cells infected with Epstein Barr virus. Future studies will clarify the mechanisms by which B cells mediate cortical injury and treatment strategies that can target B cells in the leptomeninges and CNS parenchyma.

中文翻译：

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B细胞对多发性硬化症皮质损伤的贡献

多发性硬化症不仅与白质病变有关，还与皮层病变有关。皮质受累与更大的疾病严重程度有关，因此了解皮质病理学的潜在因素有助于确定多发性硬化症的新治疗策略。B 细胞在多发性硬化症中的关键作用已通过多发性硬化症患者 B 细胞耗竭的多项关键试验得到阐明。已在多发性硬化症的所有阶段确定存在多发性硬化症中富含 B 细胞的脑膜炎症区域。软脑膜炎症与更大程度的皮质脱髓鞘和神经元丢失以及更大的疾病严重程度相关。最近的研究已经确定了 B 细胞可能介导皮质损伤的几种潜在机制，包括抗体产生、含有神经毒性物质的细胞外囊泡和促炎细胞因子的产生。此外，B 细胞可能通过对 T 细胞、巨噬细胞或小胶质细胞的影响间接介导皮质损伤。几种动物模型复制了多发性硬化症患者的脑膜炎症和皮质损伤。在这些模型中的研究已经确定 BTK 抑制和 II 型抗 CD20 抗体是可能影响脑膜炎症的潜在药物。在多发性硬化症患者中进行的抗 CD20 单克隆抗体试验未能成功地试图消除软脑膜中的 B 细胞。针对多发性硬化症中的 B 细胞的新策略包括 BTK 抑制和针对感染 Epstein Barr 病毒的 B 细胞的基于细胞的疗法。未来的研究将阐明 B 细胞介导皮质损伤的机制以及可以靶向软脑膜和 CNS 实质中 B 细胞的治疗策略。