{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:51:29Z","timestamp":1793238689442,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T follicular helper (TFH) cells are critical initiators in the development of T cell-dependent humoral immunity and the generation of protective immunity. We demonstrate that TFH cell accumulation and Ab production are negatively regulated by B7-H1 (programmed death ligand 1) in response to both helminth infection and active immunization. Following immunization of B7-H1\u2212\/\u2212 mice with keyhole limpet hemocyanin or helminth Ags, there is a profound increase in induction of TFH cells as a result of increased cell cycling and decreased apoptosis relative to wild-type mice. The increase in TFH cells in the absence of B7-H1 was associated with significant elevations in Ag-specific Ig response. Cotransfer experiments in vivo demonstrated that B7-H1 expression on B cells was required for negatively regulating TFH cell expansion and production of Ag-specific Ig. Treatment of immunized wild-type mice with anti\u2013B7-H1 or anti-programmed death 1 mAbs, but not anti\u2013B7-DC, led to a significant expansion of the TFH cell population and an enhanced Ag-specific Ig response. Our results demonstrate that the coinhibitory B7-H1\/programmed death 1 pathway can limit the expansion of TFH cells and constrain Ag-specific Ig responses. This finding has direct implications for investigations examining the feasibility of therapeutically manipulating this pathway and reveals new insights into the regulation of the humoral immune response.<\/jats:p>","DOI":"10.4049\/jimmunol.1003161","type":"journal-article","created":{"date-parts":[[2011,4,14]],"date-time":"2011-04-14T02:19:53Z","timestamp":1302747593000},"page":"5648-5655","source":"Crossref","is-referenced-by-count":125,"title":["Blockade of B7-H1 (Programmed Death Ligand 1) Enhances Humoral Immunity by Positively Regulating the Generation of T Follicular Helper Cells"],"prefix":"10.1093","volume":"186","author":[{"given":"Emily","family":"Hams","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine, St. James\u2019s Hospital, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"McCarron","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, St. James\u2019s Hospital, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Amu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, St. James\u2019s Hospital, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Bunkyo-ku, Tokyo 113-8421 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University , Bunkyo-ku, Tokyo 113-8549 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Johns Hopkins University School of Medicine , Baltimore, MD 21231"},{"name":"Institute for Cell Engineering, The Johns Hopkins University School of Medicine , Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padraic G","family":"Fallon","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, St. James\u2019s Hospital, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Our Lady\u2019s Children\u2019s Hospital , Crumlin, Dublin 12 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,15]]},"reference":[{"key":"2025032411264874700_r1","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1178334","article-title":"Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells","volume":"327","author":"O\u2019Shea","year":"2010","journal-title":"Science"},{"key":"2025032411264874700_r2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nri2644","article-title":"New insights into the differentiation and function of T follicular helper cells","volume":"9","author":"King","year":"2009","journal-title":"Nat. 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