{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:32:53Z","timestamp":1790627573346,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"15","funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["K08AI114968"],"award-info":[{"award-number":["K08AI114968"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["RO1AI114588"],"award-info":[{"award-number":["RO1AI114588"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,6]]},"abstract":"<jats:p>T follicular helper (Tfh) cell migration into germinal centers (GCs) is essential for the generation of GC B cells and antibody responses to T cell\u2013dependent (TD) antigens. This process requires interactions between lymphocyte function\u2013associated antigen 1 (LFA-1) on Tfh cells and ICAMs on B cells. The mechanisms underlying defective antibody responses to TD antigens in DOCK8 deficiency are incompletely understood. We show that mice selectively lacking DOCK8 in T cells had impaired IgG antibody responses to TD antigens, decreased GC size, and reduced numbers of GC B cells. However, they developed normal numbers of Tfh cells with intact capacity for driving B cell differentiation into a GC phenotype in vitro. Notably, migration of DOCK8-deficient T cells into GCs was defective. Following T cell receptor (TCR)\/CD3 ligation, DOCK8-deficient T cells had impaired LFA-1 activation and reduced binding to ICAM-1. Our results therefore indicate that DOCK8 is important for LFA-1\u2013dependent positioning of Tfh cells in GCs, and thereby the generation of GC B cells and IgG antibody responses to TD antigen.<\/jats:p>","DOI":"10.1172\/jci.insight.134508","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T12:30:28Z","timestamp":1592915428000},"source":"Crossref","is-referenced-by-count":21,"title":["DOCK8 is essential for LFA-1\u2013dependent positioning of T follicular helper cells in germinal centers"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-2550","authenticated-orcid":true,"given":"Erin","family":"Janssen","sequence":"first","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Tohme","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Butts","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Giguere","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard Medical School, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Sage","sequence":"additional","affiliation":[{"name":"Transplantation Research Center, Renal Division, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco E.","family":"Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Brigham and Women\u2019s Hospital, Departments of Pathology and Medicine, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8834-4929","authenticated-orcid":true,"given":"Christy","family":"Kam","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Milin","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrinmoy","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7047-076X","authenticated-orcid":true,"given":"Ali","family":"Sobh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Mansoura University Children\u2019s Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-2629","authenticated-orcid":true,"given":"Salem","family":"Al-Tamemi","sequence":"additional","affiliation":[{"name":"Sultan Qaboos University Hospital, Muscat, Oman."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7100-4103","authenticated-orcid":true,"given":"Francis W.","family":"Luscinskas","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Brigham and Women\u2019s Hospital, Departments of Pathology and Medicine, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo","family":"Batista","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard Medical School, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7394-4457","authenticated-orcid":true,"given":"Raif S.","family":"Geha","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"issue":"1","key":"B1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/imr.12740","article-title":"T follicular helper cell heterogeneity: time, space, and function","volume":"288","author":"Song","year":"2019","journal-title":"Immunol Rev"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2017.00489","article-title":"Heterogeneity of phenotype and function reflects the multistage development of T follicular helper cells","volume":"8","author":"Tr\u00fcb","year":"2017","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4927"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.023"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature12058"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1553"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270106"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2014.05.002"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171129"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090209"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1257861"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.024"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091777"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090313"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241680"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.032"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2305"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905506"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.038"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1820"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.00715","article-title":"Non-classical B cell memory of allergic IgE responses","volume":"10","author":"Saunders","year":"2019","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.001001"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.12.004"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102477"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.025"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.589"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nri3804"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.68"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.022"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.05.005"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.11.1545"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.8.1123"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1877"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3554"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.01.010"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903505"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90073-6"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.3994"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nature07345"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.015"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12518"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.226837"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2008.12.001"},{"issue":"3","key":"B44","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/j.2040-4603.2012.tb00450.x","article-title":"Claudins and other tight junction proteins","volume":"2","author":"G\u00fcnzel","year":"2012","journal-title":"Compr Physiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2010.0112"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4161\/bioa.21791"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv497"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6478"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1984"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646623"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1715"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/341619a0"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807207200"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw6433"},{"issue":"7","key":"B55","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.4049\/jimmunol.162.7.3749","article-title":"Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product","volume":"162","author":"Hoshino","year":"1999","journal-title":"J Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021340"},{"key":"B57","doi-asserted-by":"crossref","DOI":"10.1038\/s41541-018-0089-x","article-title":"Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want","volume":"3","author":"HogenEsch","year":"2018","journal-title":"NPJ Vaccines"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071087"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0412177"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2015.02.009"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12737"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94298"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85774"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110345"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202792"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2012.03620.x"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.088"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7707"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.018"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2498-1_13"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131666"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-01-0063"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101647"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/134508\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:11:15Z","timestamp":1779192675000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/134508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,6]]},"references-count":73,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8,6]]},"published-print":{"date-parts":[[2020,8,6]]}},"alternative-id":["10.1172\/jci.insight.134508"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.134508","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,6]]},"article-number":"e134508"}}