{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:19:00Z","timestamp":1791566340003,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,10,27]],"date-time":"2014-10-27T00:00:00Z","timestamp":1414368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005234","name":"Office of Public Health and Science","doi-asserted-by":"publisher","award":["AI096949"],"award-info":[{"award-number":["AI096949"]}],"id":[{"id":"10.13039\/100005234","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005234","name":"Office of Public Health and Science","doi-asserted-by":"publisher","award":["AI102680"],"award-info":[{"award-number":["AI102680"]}],"id":[{"id":"10.13039\/100005234","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>The majority of CXCR5<jats:sup>+<\/jats:sup>PD1<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T follicular helper (Tfh) cells (&gt;90%) are CD25<jats:sup>\u2212<\/jats:sup>Bcl6<jats:sup>hi<\/jats:sup>, while a small subpopulation (&lt;10%) are CD25<jats:sup>+<\/jats:sup>Bcl6<jats:sup>low<\/jats:sup> but do not express FoxP3 and are not T regulatory cells. We purified T:B\u2010cell conjugates from tonsils and found they were enriched for the CD25<jats:sup>+<\/jats:sup>Bcl6<jats:sup>low<\/jats:sup> Tfh\u2010cell subpopulation. In response to IL\u20102, these CD25<jats:sup>+<\/jats:sup> Tfh cells increased expression of costimulatory molecules ICOS or OX40, upregulated transcription factor cMaf, produced cytokines IL\u201021, IL\u201017, and IL\u201010, and raised the levels of antiapoptotic protein Bcl2. Conjugates formed with CD25<jats:sup>+<\/jats:sup>BCl6<jats:sup>low<\/jats:sup> Tfh cells included B\u00a0cells expressing higher levels of activation\u2010induced cytidine deaminase (AID), memory marker CD45RO, surface IgG or IgA, and MHC class II compared to B\u2010cell conjugates including CD25<jats:sup>\u2212<\/jats:sup>Bcl6<jats:sup>hi<\/jats:sup> Tfh cells. While IL\u20102 suppresses early Tfh\u2010cell differentiation, Tfh\u2010cell recognition of antigen\u2010presenting B\u00a0cells and signaling through the T\u2010cell receptor likely triggers expression of the high\u2010affinity IL\u20102 receptor and responses to IL\u20102 including downregulation of Bcl6. CD25 expression on Tfh cells and local production of IL\u20102 in tonsil or lymph node may support B helper T\u2010cell function during later stages of B\u2010cell maturation and the development of immune memory.<\/jats:p>","DOI":"10.1002\/eji.201444911","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T09:41:21Z","timestamp":1411810881000},"page":"298-308","source":"Crossref","is-referenced-by-count":28,"title":["CD25<sup>+<\/sup>Bcl6<sup>low<\/sup> T follicular helper cells provide help to maturing B\u00a0cells in germinal centers of human tonsil"],"prefix":"10.1002","volume":"45","author":[{"given":"Haishan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Human Virology and Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. David","family":"Pauza","sequence":"additional","affiliation":[{"name":"Institute of Human Virology and Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3128"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1553"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.12.1373"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1545"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12910"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120994"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2242"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-11-4494"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5099"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.1.68"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103246"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242540"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8180"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002828"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1690"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1715"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241680"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111174"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.02.012"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.01.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.324046"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.4049\/jimmunol.161.9.4618","article-title":"Evidence for a critical role for IL\u20102 in CD40\u2010mediated activation of naive B\u00a0cells by primary CD4 T cells","volume":"161","author":"Johnson\u2010Leger C.","year":"1998","journal-title":"J. Immunol."},{"key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.4049\/jimmunol.134.5.3104","article-title":"Induction of IgG secretion in a human B\u00a0cell clone with recombinant IL 2","volume":"134","author":"Kishi H.","year":"1985","journal-title":"J. Immunol."},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.4049\/jimmunol.144.2.562","article-title":"IL\u20102 dependence of the promotion of human B\u00a0cell differentiation by IL\u20106 (BSF\u20102)","volume":"144","author":"Splawski J. B.","year":"1990","journal-title":"J. Immunol."},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-12-53"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2426"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2425"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.6.1625"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116977"},{"key":"e_1_2_7_34_1","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.4049\/jimmunol.154.9.4341","article-title":"The role of IL\u201010 in human B\u00a0cell activation, proliferation, and differentiation","volume":"154","author":"Itoh K.","year":"1995","journal-title":"J. Immunol."},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1552"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni0208-124"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009234107"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1631559"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002354"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909639"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3484"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900123"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.218867"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-088666"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-10-60"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100898108"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.025"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2010.03343.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209471200"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075032"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)00405-7"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.12.010"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/35078099"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.02.009"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1585"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002920"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2007.01985.x"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-087767"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201444911","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201444911","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T17:40:59Z","timestamp":1694281259000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201444911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,27]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/eji.201444911"],"URL":"https:\/\/doi.org\/10.1002\/eji.201444911","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,27]]}}}