言語種別	英語
発表タイトル	A series of CD21lo B cell subsets are recruited to the CSF in the acute phase of NMO
会議名	第66回日本神経学会学術大会
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎錦織隆成, 濱谷美緒, 吉富啓之, 木村公俊, 髙田真基, 芦田真士, 藤井ちひろ, 越智博文, 松本理器, 高橋良輔, 近藤誉之, 上野英樹
発表年月日	2025/05/23
開催地 （都市, 国名）	大阪
開催期間	2025/05/21～2025/05/24
概要	[Objectives] NMO is an acute inflammatory demyelinating disease, and AQP4-IgG in blood is crucial for its diagnosis. Previous studies show AQP4-IgG directly causes CNS inflammation, with B cells being central to NMO pathology. In this study, we elucidated where and how B cell response is altered in patients with NMO (pwNMO). [Methods] We comprehensively analyzed with 33-parameter flow cytometry the immune cell populations in CSF-blood paired samples obtained from acute-phase pwNMO (n=8), and compared to those from patients with acute-phase MS (n=10) and neurological disease controls (n=27). [Results] The frequency of antibody-secreting cells (ASC) and a series of CD21lo B cell subsets ranging from "activated" naïve, double negative, and switched memory were dominant in CSF of pwNMO. A majority of these CD21lo B cell subsets expressed CD69 and CXCR3, suggesting their CNS residency. Two B helper T cell subsets highly expressing CD69 and CXCR3 were enriched in CSF of pwNMO, suggesting their interactions with ASC precursors in the CNS. We further analyzed non-acute CSF and blood samples and found that an increase of CD21lo memory B subsets was also observed in the CSF of treatment-refractory pwNMO, and that ASCs derived from CD21lo memory B cells were more likely to express CXCR3 and CD138 in vitro and could produce AQP4-IgG. [Conclusion] Our study highly suggests that the mechanism to promote the generation of CD21lo B cells, thus the extrafollicular pathway, becomes activated during the acute phase of NMO, and generated CD21lo B cell subsets contribute to the pathogenesis.