{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:48:48Z","timestamp":1783529328530,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074538, 82171341, 82474635"],"award-info":[{"award-number":["82074538, 82171341, 82474635"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to compare the proportions of circulating follicular helper T (Tfh) and B cell subsets, as well as serum levels of cytokines and chemokines, between patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 antibody (AQP4-ab)\u2013positive and healthy controls, and to investigate the interaction mechanisms between Tfh and B cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AQP4-ab\u2013positive NMOSD patients were enrolled during acute attacks and remission phases, along with age- and sex-matched healthy controls. Flow cytometry was used to assess circulating Tfh and B cell subsets. Purified CD19\n                      <jats:sup>+<\/jats:sup>\n                      B cells were cultured alone or co-cultured with CD4\n                      <jats:sup>+<\/jats:sup>\n                      CXCR5\n                      <jats:sup>+<\/jats:sup>\n                      Tfh cells for 6 days, with various interventions applied to evaluate alterations in Tfh or B cell phenotypes. Serum and supernatant levels of interleukin (IL)-6, IL-21, CXCL13, and AQP4-ab were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During acute attacks, NMOSD patients exhibited significantly higher proportions of total Tfh, ICOS\n                      <jats:sup>+<\/jats:sup>\n                      Tfh, activated Tfh17, switched memory B cells, double-negative B cells, plasmablasts, and plasma cells, along with elevated serum levels of IL-6, IL-21, and CXCL13. In contrast, the frequencies of activated Tfh1, naive B cells, and transitional regulatory B cell subsets were significantly reduced. Functional assays revealed that Tfh cells promoted B cell proliferation, differentiation, and AQP4-ab production. Conversely, B cell subsets enhanced Tfh cell proliferation, differentiation, and IL-21 secretion; these effects were attenuated by anti-CD20 and anti\u2013interferon-\u03b3 (IFN-\u03b3) monoclonal antibodies, but were augmented by anti\u2013IL-10 monoclonal antibody.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating Tfh and B cell subsets are dysregulated in AQP4-ab\u2013positive NMOSD, accompanied by increased levels of IL-6, IL-21, and CXCL13. Reciprocal interactions between Tfh and B cells likely contribute to disease pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1704282","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T06:35:54Z","timestamp":1767681354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Dysregulated Tfh\/B cells and their interactions in neuromyelitis optica spectrum 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