{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:05:33Z","timestamp":1782281133282,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","doi-asserted-by":"publisher","award":["T\u00dcBITAK (222S650)"],"award-info":[{"award-number":["T\u00dcBITAK (222S650)"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002657","name":"Istanbul \u00dcniversitesi","doi-asserted-by":"publisher","award":["37847"],"award-info":[{"award-number":["37847"]}],"id":[{"id":"10.13039\/501100002657","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002657","name":"Istanbul \u00dcniversitesi","doi-asserted-by":"publisher","award":["37896"],"award-info":[{"award-number":["37896"]}],"id":[{"id":"10.13039\/501100002657","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>T follicular helper (Tfh) cells regulate B\u2010cell responses within germinal centres primarily via programmed cell death protein 1 (PD\u20101) and inducible T\u2010cell costimulator (ICOS), whereas CXC chemokine receptor type 5 (CXCR5)\u2010negative T peripheral helper (Tph) cells provide similar support extra\u2010follicularly. Both subsets contribute to the pathogenesis of acetylcholine receptor\u2010antibody\u2010positive myasthenia gravis (AChR\u2010MG). This study investigated the roles of PD\u20101, ICOS and CXCR5 in T\u2010cell\u2010mediated B\u2010cell activation to identify therapeutic targets for MG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CD4 T\u00a0cells from 10 healthy controls and six untreated AChR\u2010MG patients were sorted by CXCR5, PD\u20101 and ICOS expression, stimulated with anti\u2010CD3\/CD28, and co\u2010cultured with autologous CD19 B cells. Plasmablast differentiation, total AChR\u2010IgG and cytokine productions were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In healthy donors, PD\u20101\n                      <jats:sup>+<\/jats:sup>\n                      or ICOS\n                      <jats:sup>+<\/jats:sup>\n                      Tph cells modestly enhanced plasmablasts and IgG production, while CXCR5\n                      <jats:sup>+<\/jats:sup>\n                      Tfh cells co\u2010expressing PD\u20101 or ICOS induced significantly stronger B\u2010cell responses. In AChR\u2010MG patients, PD\u20101 expressing T\u00a0cells promoted plasmablasts, antibody production and cytokine secretion regardless of CXCR5, with amplified effects in CXCR5\n                      <jats:sup>+<\/jats:sup>\n                      co\u2010cultures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      PD\u20101 expression on CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u00a0cells is associated with increased B\u2010cell helper capacity. This effect is more pronounced in Tfh\u2010related contexts and is linked to dysregulated humoral immune responses in MG. PD\u20101 appears to play a central role in the pathogenesis of MG, primarily through Tfh cell activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70112","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T23:04:43Z","timestamp":1782083083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of CXCR5, PD\u20101 and ICOS on B\u2010cell responses and relevance to myasthenia gravis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2609-467X","authenticated-orcid":false,"given":"Merve","family":"\u00c7ebi","sequence":"first","affiliation":[{"name":"Department of Physiology, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-4172","authenticated-orcid":false,"given":"Arman","family":"\u00c7akar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6426-676X","authenticated-orcid":false,"given":"Hacer","family":"Durmu\u015f","sequence":"additional","affiliation":[{"name":"Department of Neurology, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-6590","authenticated-orcid":false,"given":"Ye\u015fim","family":"Parman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-7173","authenticated-orcid":false,"given":"G\u00fcher","family":"Saruhan\u2010Direskeneli","sequence":"additional","affiliation":[{"name":"Department of Physiology, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29894"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00145-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10112235"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00212"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810"},{"key":"e_1_2_9_8_1","first-page":"1861","article-title":"Expanded circulating peripheral helper T\u00a0cells in systemic lupus erythematosus: association with disease activity and B cell differentiation","volume":"58","author":"Makiyama A","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01924"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4936-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00529-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2340"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4927"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.09.007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00809"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000945"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1545"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.012"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214382"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01637"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4100"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2015.01.014"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-014-0500-6"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.10.014"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12010130"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2024.101453"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S221340"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182232"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-6499-y"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001334"}],"container-title":["Clinical &amp; 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