{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:36:05Z","timestamp":1791354965761,"version":"4.3.1"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,6,22]],"date-time":"2006-06-22T00:00:00Z","timestamp":1150934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The generation of high\u2010affinity antibody\u2010secreting plasma cells critically depends on the presence of CD4 T cells during the germinal center (GC) reaction. GC T cells are so far incompletely characterized in terms of phenotype and function. Here, we show that human follicular B helper\u2004T (T<jats:sub>FH<\/jats:sub>) cells are characterized by high expression of the homeostatic chemokine receptor CXCR5 and the costimulatory molecule ICOS, but not CD57 expression. CXCR5<jats:sup>hi<\/jats:sup>ICOS<jats:sup>hi<\/jats:sup> CD4 T cells are the most potent inducers of IgG production that also secrete large amounts of the B cell\u2010attracting chemokine CXCL13. CXCR5<jats:sup>hi<\/jats:sup>ICOS<jats:sup>hi<\/jats:sup> CD4 T cells differ from other tonsillar CD4 T cell subsets in their stimulatory activity, proliferative capacity and susceptibility to apoptosis. Large\u2010scale gene expression analysis revealed that T<jats:sub>FH<\/jats:sub> cells are only distantly related to CXCR5<jats:sup>\u2013<\/jats:sup> and CXCR5<jats:sup>+<\/jats:sup> central memory\u2004T (T<jats:sub>CM<\/jats:sub>) as well as effector memory\u2004T (T<jats:sub>EM<\/jats:sub>) cells present in the periphery. CXCR5<jats:sup>hi<\/jats:sup>ICOS<jats:sup>hi<\/jats:sup> CD4 T cells appear to be terminally differentiated T\u2004helper cells that express a unique set of transcription factors related to the Notch signaling pathway and thus differentiate independent of other T\u2004helper cell populations.<\/jats:p><jats:p>See accompanying commentary: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1002\/eji.200636334\">http:\/\/dx.doi.org\/10.1002\/eji.200636334<\/jats:ext-link><\/jats:p>","DOI":"10.1002\/eji.200636136","type":"journal-article","created":{"date-parts":[[2006,6,22]],"date-time":"2006-06-22T11:06:34Z","timestamp":1150974394000},"page":"1892-1903","source":"Crossref","is-referenced-by-count":297,"title":["Follicular B helper T cell activity is confined to CXCR5<sup>hi<\/sup>ICOS<sup>hi<\/sup> CD4 T cells and is independent of CD57 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