早期发育的B细胞经历脑膜中枢神经系统特异性抗原的阴性选择
2021-10-14   阅读:381   来源:细胞

西湖大学徐和平、何丹阳等研究人员合作发现,早期发育的B细胞经历脑膜中枢神经系统特异性抗原的阴性选择。相关论文于2021年10月8日在线发表于国际学术期刊《免疫》。

研究人员在小鼠和非人类灵长类动物的脑膜中发现了一个连续的B细胞发育轨迹。脑膜B细胞主要位于硬脑膜窦,那里的内皮细胞表达了支持B细胞发育的基本微环境因子。异种共生实验和系谱追踪显示,脑膜发育中的B细胞是通过一个不依赖血液循环的途径从造血干细胞(HSC)衍生的祖细胞中不断补充的。识别髓鞘少突胶质细胞糖蛋白(MOG)(一种中枢神经系统特异性抗原)的自身反应性未成熟B细胞被专门从脑膜中清除。此外,Mog基因的遗传缺失恢复了脑膜中自身反应性B细胞群。

这些发现确定了脑膜是一个独特的B细胞发育库,能够原位阴性选择来确保局部无自身反应性免疫库。

据悉,自身反应性B细胞的祖细胞通过中央耐受检查点被清除,这一过程被认为仅限于哺乳动物的骨髓。

附:英文原文

Title: Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges

Author: Yan Wang, Dianyu Chen, Di Xu, Chao Huang, Ruxiao Xing, Danyang He, Heping Xu

Issue&Volume: 2021-10-08

Abstract: Self-reactive B cell progenitors are eliminated through central tolerance checkpoints,a process thought to be restricted to the bone marrow in mammals. Here, we identifieda consecutive trajectory of B cell development in the meninges of mice and non-humanprimates. The meningeal B cells were located predominantly at the dural sinuses, whereendothelial cells expressed essential niche factors to support B cell development.Parabiosis experiments together with lineage tracing showed that meningeal developingB cells were replenished continuously from hematopoietic stem cell (HSC)-derived progenitorsvia a circulation-independent route. Autoreactive immature B cells that recognizedmyelin oligodendrocyte glycoprotein (MOG), a central nervous system-specific antigen,were eliminated specifically from the meninges. Furthermore, genetic deletion of theMog gene restored the self-reactive B cell population in the meninges. These findingsidentify the meninges as a distinct reservoir for B cell development, allowing in situ negative selection to ensure a locally non-self-reactive immune repertoire.

DOI: 10.1016/j.immuni.2021.09.016

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