{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:36:00Z","timestamp":1791354960485,"version":"4.3.1"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,8,16]]},"abstract":"<jats:p>\n                    T follicular helper (Tfh) cells represent a Th subset engaged in the help of B-cell responses in germinal centers (GCs). Tfh cells abundantly express the transcription repressor B-cell lymphoma 6 (Bcl6), a factor that is necessary and sufficient for their development in vivo. Whether Tfh or Tfh-committed cells are involved in the help of B cells outside GCs remains unclear, particularly in humans. In this study, we identified a previously undefined\n                    <jats:italic>BCL6<\/jats:italic>\n                    -expressing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell subset in human tonsils. This subset expressed IL-7 receptor and chemokine receptor 5 (CXCR5) and inducible costimulator (ICOS) at low levels (CXCR5\n                    <jats:sup>lo<\/jats:sup>\n                    ICOS\n                    <jats:sup>lo<\/jats:sup>\n                    ), and it was found exclusively outside GCs. CXCR5\n                    <jats:sup>lo<\/jats:sup>\n                    ICOS\n                    <jats:sup>lo<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells secreted larger amounts of IL-21 and IL-10 than CXCR5\n                    <jats:sup>hi<\/jats:sup>\n                    ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    GC-Tfh cells upon activation, and they induced proliferation and differentiation of na\u00efve B cells into Ig-producing cells more efficiently than GC-Tfh cells. However, this subset lacked the capacity to help GC-B cells because of the induction of apoptosis of GC-B cells through the FAS\/FAS\u2013ligand interaction. CXCR5\n                    <jats:sup>lo<\/jats:sup>\n                    ICOS\n                    <jats:sup>lo<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells expressed equivalent amounts of\n                    <jats:italic>BCL6<\/jats:italic>\n                    transcript with CXCR5\n                    <jats:sup>hi<\/jats:sup>\n                    ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    GC-Tfh cells, but they expressed less Bcl6 protein. Collectively, our study indicates that CXCR5\n                    <jats:sup>lo<\/jats:sup>\n                    ICOS\n                    <jats:sup>lo<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in human tonsils represent Tfh lineage-committed cells that provide help to na\u00efve and memory B cells outside GCs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1100898108","type":"journal-article","created":{"date-parts":[[2011,8,2]],"date-time":"2011-08-02T00:20:20Z","timestamp":1312244420000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":139,"title":["Human tonsil\n                    <i>B<\/i>\n                    -\n                    <i>cell lymphoma 6<\/i>\n                    (\n                    <i>BCL6<\/i>\n                    )-expressing CD4\n                    <sup>+<\/sup>\n                    T-cell subset specialized for B-cell help outside germinal centers"],"prefix":"10.1073","volume":"108","author":[{"given":"Salah-Eddine","family":"Bentebibel","sequence":"first","affiliation":[{"name":"Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;"},{"name":"Institute of Biomedical Studies, Baylor University,Waco, TX 76798; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Banchereau","sequence":"additional","affiliation":[{"name":"Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U899, Center for Human Vaccines, Dallas, TX, 75204"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ueno","sequence":"additional","affiliation":[{"name":"Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U899, Center for Human Vaccines, Dallas, TX, 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