From the China National Clinical Research Center for Neurological Diseases (C.Z., Y.W., F.-D.S.), Beijing Tiantan Hospital, Capital Medical University; and Department of Neurology (C.Z., T.-X.Z., Y.L., D.J., P.Z., C.D., M.Y., Q.L., F.-D.S.), Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin Medical University, China.
Neurol Neuroimmunol Neuroinflamm. 2021 Aug 31;8(6). doi: 10.1212/NXI.0000000000001070. Print 2021 Nov.
To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD).
We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD.
Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes ( and ). Circulating B cells display an increase of antigen presentation markers ( and ), as well as activation signatures (, , and ). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by genes and synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti-aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19 and CD19 ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD.
B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.
评估视神经脊髓炎谱系疾病（NMOSD）患者不同部位 B 细胞亚群的分子特征。
通过单细胞 RNA 测序，我们对 NMOSD 患者的脑脊液、血液和骨髓中的 B 细胞转录组谱进行了分析。
在所测试的组织类型中，鉴定出了 4 种具有不同特征的主要 B 细胞亚群：幼稚 B 细胞、记忆 B 细胞、年龄相关 B 细胞和分泌抗体的细胞（ASCs）。NMOSD B 细胞表现出促炎活性和趋化因子受体基因（和）的表达增加。循环 B 细胞显示出抗原呈递标记物（和）的增加，以及激活标记物（、和）的增加。相比之下，骨髓 B 细胞群体包含大量 ASC 亚群，其氧化和代谢活性增加，反映在基因和合成酶基因上。通常，NMOSD B 细胞对 I 型干扰素高度敏感，这促进了 B 细胞成熟和抗水通道蛋白 4 自身抗体的产生。NMOSD 患者血液和脑脊液中的 ASC 池显著升高。CD19 和 CD19+ ASCs 均可被托珠单抗清除，但 NMOSD 患者的利妥昔单抗治疗无效。
B 细胞在 NMOSD 中针对自身反应进行了精细的调节，并对 I 型干扰素产生过度反应。抑制 I 型干扰素通路可能为 NMOSD 提供新的治疗途径。
