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Deciphering the signals that induce IL\u201021 production in CD4<jats:sup>+<\/jats:sup> T cells and those triggered by IL\u201021 in B cells are, therefore, of importance for understanding the generation of antibody (Ab) responses. Here, we show that IL\u20106 increased IL\u201021 production by human CD4<jats:sup>+<\/jats:sup> T cells, particularly in those that express the transcriptional regulator B cell lymphoma (BCL)6, which is required in mice for the development of C\u2010X\u2010C chemokine receptor type 5 (CXCR5<jats:sup>+<\/jats:sup>) IL\u201021\u2010producing T follicular helper (T<jats:sub>FH<\/jats:sub>) cells. However, retroviral overexpression of BCL6 in total human CD4<jats:sup>+<\/jats:sup> T cells only transiently increased CXCR5, the canonical T<jats:sub>FH<\/jats:sub>\u2010defining surface marker. We show here that IL\u201021 was required for the induction of Ab production by IL\u20106. In IL\u201021\u2010treated B cells, signal transducer and activator of transcription (STAT)3 was required for optimal immunoglobulin production and upregulation of PR domain containing 1 (<jats:italic>PRDM1<jats:sup>+<\/jats:sup><\/jats:italic>), the master plasma cell factor. These results, therefore, demonstrate the critical importance of STAT3 activation in B cells during IL\u201021\u2010driven humoral immunity and suggest that BCL6 expression, although not sufficient, may serve as a platform for the acquisition of a T<jats:sub>FH<\/jats:sub>\u2010like phenotype by human CD4<jats:sup>+<\/jats:sup> T cells.<\/jats:p>","DOI":"10.1038\/icb.2012.17","type":"journal-article","created":{"date-parts":[[2012,4,10]],"date-time":"2012-04-10T14:39:57Z","timestamp":1334068797000},"page":"802-811","source":"Crossref","is-referenced-by-count":108,"title":["IL\u20106 Triggers IL\u201021 production by human CD4<sup>+<\/sup> T cells to drive STAT3\u2010dependent plasma cell differentiation in B cells"],"prefix":"10.1111","volume":"90","author":[{"given":"Sean A","family":"Diehl","sequence":"first","affiliation":[{"name":"Department of Medicine\u2010Immunobiology, University of Vermont  Burlington VT USA"},{"name":"Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam (AMC\u2010UvA), Center for Immunology Amsterdam (CIA)  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Schmidlin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam (AMC\u2010UvA), Center for Immunology Amsterdam (CIA)  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam (AMC\u2010UvA), Center for Immunology Amsterdam (CIA)  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam 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