Anti-CD20 B cell depleting therapies have demonstrated that these cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges in MS and also some chronic animal models of disease, typically adjacent to demyelinating lesions. The role of these meningeal B cells in disease is not known, nor is their susceptibility to anti-CD20 therapy. Here, we administered anti-CD20 to 2D2 IgHMOG spontaneous experimental autoimmune encephalomyelitis mice in the chronic phase of disease, after the establishment of meningeal B cell clusters. Compared to the circulation, lymph nodes, and spleen, B cell depletion from the CNS was delayed and not evident until 7d post administration of anti-CD20. Further, we did not find evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. The reduction of B cell numbers in the CNS coincided with less demyelination of the spinal cord white matter and also, surprisingly, an increase in the number of T cells recruited to the meninges but not parenchyma.

中文翻译：

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在中枢神经系统自身免疫性慢性模型中，系统性给予抗CD20可以间接减少发炎的脑膜中的B细胞

抗CD20 B细胞耗竭疗法已证明，这些细胞是多发性硬化症疾病进展的重要驱动器，尽管其致病机理尚不清楚。大量B细胞聚集在MS的发炎脑膜以及一些慢性疾病动物模型中，通常与脱髓鞘病变相邻。这些脑膜B细胞在疾病中的作用尚不清楚，它们对抗CD20治疗的敏感性也未知。在这里，在建立脑膜B细胞簇后，我们在疾病的慢性期向2D2 IgHMOG自发实验性自身免疫性脑脊髓炎小鼠施用了抗CD20。与循环，淋巴结和脾脏相比，中枢神经系统的B细胞耗竭被延迟，直到抗CD20给药后7天才明显。进一步，我们没有发现抗CD20直接进入脑膜B细胞的证据，而是耗竭是间接的，并且是脑膜种群持续更新和消除维持其外周血池的结果。中枢神经系统中B细胞数量的减少与脊髓白质的脱髓鞘减少同时，令人惊讶的是，募集到脑膜而不是实质细胞的T细胞数量增加。