{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:01:53Z","timestamp":1793109713345,"version":"4.5.0"},"reference-count":63,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,11,24]]},"abstract":"<jats:p>The role of specialized follicular helper T (TFH) cells in the germinal center has become well recognized, but it is less clear how effector T cells govern the extrafollicular response, the dominant pathway of high-affinity, isotype-switched autoantibody production in the MRL\/MpJ-Faslpr (MRLlpr) mouse model of lupus. MRLlpr mice lacking the Icos gene have impaired extrafollicular differentiation of immunoglobulin (Ig) G+ plasma cells accompanied by defects in CXC chemokine receptor (CXCR) 4 expression, interleukin (IL) 21 secretion, and B cell helper function in CD4 T cells. These phenotypes reflect the selective loss of a population of T cells marked by down-regulation of P-selectin glycoprotein ligand 1 (PSGL-1; also known as CD162). PSGL-1lo T cells from MRLlpr mice express CXCR4, localize to extrafollicular sites, and uniquely mediate IgG production through IL-21 and CD40L. In other autoimmune strains, PSGL-1lo T cells are also abundant but may exhibit either a follicular or extrafollicular phenotype. Our findings define an anatomically distinct extrafollicular population of cells that regulates plasma cell differentiation in chronic autoimmunity, indicating that specialized humoral effector T cells akin to TFH cells can occur outside the follicle.<\/jats:p>","DOI":"10.1084\/jem.20080840","type":"journal-article","created":{"date-parts":[[2008,11,4]],"date-time":"2008-11-04T01:58:40Z","timestamp":1225763920000},"page":"2873-2886","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":384,"title":["ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity"],"prefix":"10.1084","volume":"205","author":[{"given":"Jared M.","family":"Odegard","sequence":"first","affiliation":[{"name":"1Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"Marks","sequence":"additional","affiliation":[{"name":"1Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah D.","family":"DiPlacido","sequence":"additional","affiliation":[{"name":"1Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C.","family":"Poholek","sequence":"additional","affiliation":[{"name":"2Department of Cell Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight H.","family":"Kono","sequence":"additional","affiliation":[{"name":"5Department of Immunology and Microbial Sciences, Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Dong","sequence":"additional","affiliation":[{"name":"1Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"1Department of Immunobiology"},{"name":"3Howard Hughes Medical Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Craft","sequence":"additional","affiliation":[{"name":"1Department of Immunobiology"},{"name":"4Section of Rheumatology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,11,3]]},"reference":[{"key":"2023072916351745300_BIB1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.coi.2006.03.003","volume":"18","year":"2006","journal-title":"Curr. 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