B cells and their progenitors reside in homeostatic meninges

The central nervous system (CNS) is ensheathed by the meninges and cerebrospinal fluid. Recent findings suggest complex immunological functions of these CNS-associated border tissues. Unlike myeloid lineage cells, lymphocytes in border compartments have been largely disregarded in previous studies. Based on single cell transcriptomics, we here identified a highly location-specific composition and expression profile of tissue-resident leukocytes in every border compartment. Only the dura layer of the meninges contained a large population of B cells under homeostatic conditions in multiple species. Murine dura B cells exhibited slow turnover, long-term tissue residency and matured in experimental neuroinflammation. The dura also contained B lineage progenitors at the pro-B cell stage unexpected outside of bone marrow, without direct influx from the periphery or the skull bone marrow. This identifies the dura as an unexpected site of B cell residence and potentially development in homeostasis and neuroinflammation.中枢神经系统（central nervous system, CNS）由脑膜与脑脊液包被。近期研究揭示，此类中枢神经系统相关边界组织具备复杂的免疫学功能。相较于髓系细胞，边界区域内的淋巴细胞在既往研究中长期未受到足够重视。本研究基于单细胞转录组学技术，明确了各边界区域内组织驻留白细胞的高度位置特异性组成与基因表达谱。在稳态条件下，多个物种中仅脑膜的硬脑膜层含有大量B细胞群。小鼠硬脑膜内的B细胞更新速率缓慢、可长期驻留组织，并在实验性神经炎症中趋于成熟。此外，硬脑膜中还存在骨髓外罕见的前B细胞阶段B系祖细胞，此类祖细胞并非由外周循环或颅骨骨髓直接迁移而来。本研究证实，硬脑膜是一个此前未被认知的B细胞驻留位点，且在稳态与神经炎症状态下可能具备B细胞发育的潜能。