{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360589016531327488.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1093/brain/awaf086"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awaf086/62278341/awaf086.pdf"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/brain/article-pdf/148/8/2995/62278341/awaf086.pdf"}}],"dc:title":[{"@value":"CD21lo B-cell subsets are recruited to the central nervous system in acute neuromyelitis optica"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n               <jats:p>Neuromyelitis optica (NMO) is an acute inflammatory demyelinating disease of the CNS. The presence of astrocyte-targeted AQP4-immunoglobulin G (IgG) in peripheral blood is a major factor in its diagnosis. Previous studies show that AQP4-IgG contributes directly to CNS inflammation and that B cells play a central pathogenic role in NMO. However, where and how the B-cell response is altered remains controversial.</jats:p>\n               <jats:p>In this study, we used high-parameter flow cytometry to carry out a comprehensive analysis of the immune cell populations in the CSF samples obtained from first-episode acute-phase NMO patients, compared with those from patients with acute-phase multiple sclerosis and other neurological diseases. Among 10 immune cell populations defined in the analysis, the frequency only of B cells and antibody-secreting cells (ASC) was higher in the CSF of acute-phase NMO compared with other neurological diseases. Detailed assessments of B-cell and ASC subsets in the CSF revealed differences in the dominant subsets between NMO and multiple sclerosis. In NMO, a series of CD21lo B-cell subsets, including ‘activated’ naïve B, double-negative and switched memory subsets, considered as ASC precursors, were dominant. A majority of these CD21lo B-cell subsets expressed CD69 and CXCR3, suggesting their CNS residency. An increase of CD21lo B-cell subsets was also observed in the CSF of treatment-refractory NMO patients. Furthermore, two B-helper T-cell subsets, T peripheral helper type 1 and T follicular helper type 1 cells, both highly expressing CD69 and CXCR3, were enriched in the CSF of NMO patients, suggesting their interactions with ASC precursors in the CNS.</jats:p>\n               <jats:p>In vitro culture experiments using blood samples from patients with NMO showed that CD21lo B cells included AQP4-IgG-producing cells and displayed a high propensity to differentiate into ASCs. We also found that CD21lo B-cell subsets in NMO upregulated the expression of C5a receptors, and C5a signals promoted their differentiation into ASCs. ASCs derived from CD21lo B cells expressed high levels of CXCR3 and CD138. The increase in CD21lo B-cell subsets was significantly correlated with the annual relapse rate.</jats:p>\n               <jats:p>Collectively, our study strongly suggests that the mechanism to promote the generation of CD21lo B cells, probably via the extrafollicular pathway, becomes activated during the acute phase of NMO and that the generated CD21lo B-cell subsets contribute to the pathogenesis. Targeting CD21lo B-cell subsets might be useful for the development of novel therapeutic approaches.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380589016531327490","@type":"Researcher","foaf:name":[{"@value":"Ryusei Nishigori"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Kyoto University Graduate School of Medicine , Kyoto 6068507 ,"},{"@value":"Department of Immunology, Kyoto University Graduate School of Medicine , Kyoto 6068501 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327493","@type":"Researcher","foaf:name":[{"@value":"Mio Hamatani"}],"jpcoar:affiliationName":[{"@value":"Institute for the Advanced Study of Human Biology, Kyoto University , Kyoto 6068501 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327489","@type":"Researcher","foaf:name":[{"@value":"Hiroyuki Yoshitomi"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology, Kyoto University Graduate School of Medicine , Kyoto 6068501 ,"},{"@value":"Institute for the Advanced Study of Human Biology, Kyoto University , Kyoto 6068501 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327496","@type":"Researcher","foaf:name":[{"@value":"Kimitoshi Kimura"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Kyoto University Graduate School of Medicine , Kyoto 6068507 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327497","@type":"Researcher","foaf:name":[{"@value":"Masaki Takata"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Kyoto University Graduate School of Medicine , Kyoto 6068507 ,"},{"@value":"Department of Immunology, Kyoto University Graduate School of Medicine , Kyoto 6068501 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327488","@type":"Researcher","foaf:name":[{"@value":"Shinji Ashida"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 6028566 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327498","@type":"Researcher","foaf:name":[{"@value":"Chihiro Fujii"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Kansai Medical University Medical Center , Moriguchi 5708507 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327491","@type":"Researcher","foaf:name":[{"@value":"Hirofumi Ochi"}],"jpcoar:affiliationName":[{"@value":"Department of Intractable Disease and Aging Science, Ehime University Graduate School of Medicine , Ehime 7910295 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327495","@type":"Researcher","foaf:name":[{"@value":"Ryosuke Takahashi"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Kyoto University Graduate School of Medicine , Kyoto 6068507 ,"},{"@value":"Kyoto University Research Administration Center, Kyoto University , Kyoto 6068501 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327492","@type":"Researcher","foaf:name":[{"@value":"Takayuki Kondo"}],"jpcoar:affiliationName":[{"@value":"Department of Neurology, Kansai Medical University Medical Center , Moriguchi 5708507 ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380589016531327494","@type":"Researcher","foaf:name":[{"@value":"Hideki Ueno"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology, Kyoto University Graduate School of Medicine , Kyoto 6068501 ,"},{"@value":"Institute for the Advanced Study of Human Biology, Kyoto University , Kyoto 6068501 ,"},{"@value":"Kyoto University Immunomonitoring Center, Kyoto University , Kyoto 6068501 ,"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00068950"},{"@type":"EISSN","@value":"14602156"}],"prism:publicationName":[{"@value":"Brain"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2025-03-05","prism:volume":"148","prism:number":"8","prism:startingPage":"2995","prism:endingPage":"3010"},"reviewed":"false","dc:rights":["https://academic.oup.com/pages/standard-publication-reuse-rights"],"url":[{"@id":"https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awaf086/62278341/awaf086.pdf"},{"@id":"https://academic.oup.com/brain/article-pdf/148/8/2995/62278341/awaf086.pdf"}],"createdAt":"2025-03-05","modifiedAt":"2025-08-01","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390870297797552128","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Progress in the Treatment of Neuromyelitis Optica Spectrum Disorder: From Pathogenic Insights to Biologics"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1093/brain/awaf086"},{"@type":"CROSSREF","@value":"10.2169/internalmedicine.6772-25_references_DOI_V0F5pa0k6xSpZS2MlW7Af9K4OpK"}]}