{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:36:50Z","timestamp":1792701410413,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,5,29]]},"abstract":"<jats:p>\n                    Follicular T-helper (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) cells cooperate with GL7\n                    <jats:sup>+<\/jats:sup>\n                    CD95\n                    <jats:sup>+<\/jats:sup>\n                    germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T\n                    <jats:sub>FH<\/jats:sub>\n                    cell differentiation and GC formation. After immunization with protein or infection with the protozoon\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    , draining lymph nodes (LNs) of IFN-regulatory factor-4 (\n                    <jats:italic>\n                      Irf4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer\u2019s patches of naive\n                    <jats:italic>\n                      Irf4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Accordingly, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the LNs and Peyer\u2019s patches failed to express the T\n                    <jats:sub>FH<\/jats:sub>\n                    key transcription factor B-cell lymphoma-6 and other T\n                    <jats:sub>FH<\/jats:sub>\n                    -related molecules. During chronic leishmaniasis, the draining\n                    <jats:italic>\n                      Irf4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    LNs disappeared because of massive cell death. Adoptive transfer of WT CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells or few\n                    <jats:italic>L. major<\/jats:italic>\n                    primed WT T\n                    <jats:sub>FH<\/jats:sub>\n                    cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity,\n                    <jats:italic>\n                      Irf4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    T\n                    <jats:sub>FH<\/jats:sub>\n                    cell differentiation was not rescued by close neighborhood to transferred WT T\n                    <jats:sub>FH<\/jats:sub>\n                    cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell\u2013dependent antigens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1205834109","type":"journal-article","created":{"date-parts":[[2012,5,3]],"date-time":"2012-05-03T00:32:31Z","timestamp":1336005151000},"page":"8664-8669","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":184,"title":["Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation"],"prefix":"10.1073","volume":"109","author":[{"given":"Nadine","family":"Bollig","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Br\u00fcstle","sequence":"additional","affiliation":[{"name":"Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, ON, Canada M5G 2C1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Kellner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waltraud","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zytobiologie, Universit\u00e4t Marburg, 35037 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elfadil","family":"Abass","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmann","family":"Raifer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e4rbel","family":"Camara","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Brendel","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin, Universit\u00e4t Marburg, 35043 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Giel","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin, Universit\u00e4t Marburg, 35043 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evita","family":"Bothur","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Huber","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Paul","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Elli","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zytobiologie, Universit\u00e4t Marburg, 35037 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Kroczek","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Immunologie, Robert-Koch-Institut, 13353 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Nurieva","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77054; 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