{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:01:30Z","timestamp":1791302490691,"version":"4.1.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"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":[[2007,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations in SH2D1A resulting in lack of SLAM-associated protein (SAP) expression cause the human genetic immunodeficiency X-linked lymphoproliferative disease. A severe block in germinal center development and lack of long-term humoral immunity is one of the most prominent phenotypes of SAP\u2212 mice. We show, in this study, that the germinal center block is due to an essential requirement for SAP expression in Ag-specific CD4 T cells to develop appropriate follicular helper T cell functions. It is unknown what signaling molecules are involved in regulation of SAP-dependent CD4 T cell help functions. SAP binds to the cytoplasmic tail of SLAM, and we show that SLAM is expressed on resting and activated CD4 T cells, as well as germinal center B cells. In addition, SAP can recruit Fyn kinase to SLAM. We have now examined the role(s) of the SLAM-SAP-Fyn signaling axis in in vivo CD4 T cell function and germinal center development. We observed normal germinal center development, long-lived plasma cell development, and Ab responses in SLAM\u2212\/\u2212 mice after a viral infection (lymphocytic choriomeningitis virus). In a separate series of experiments, we show that SAP is absolutely required in CD4 T cells to drive germinal center development, and that requirement does not depend on SAP-Fyn interactions, because CD4 T cells expressing SAP R78A are capable of supporting normal germinal center development. Therefore, a distinct SAP signaling pathway regulates follicular helper CD4 T cell differentiation, separate from the SLAM-SAP-Fyn signaling pathway regulating Th1\/Th2 differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.178.2.817","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:51Z","timestamp":1397848671000},"page":"817-828","source":"Crossref","is-referenced-by-count":93,"title":["SAP Regulation of Follicular Helper CD4 T Cell Development and Humoral Immunity Is Independent of SLAM and Fyn Kinase"],"prefix":"10.1093","volume":"178","author":[{"given":"Megan M","family":"McCausland","sequence":"first","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isharat","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics and Immunology, Princess Margaret Hospital , Toronto ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Virology, Faculty of Medicine, Kyushu University , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Crotty","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,1,15]]},"reference":[{"key":"2026012809421138400_R1","first-page":"129","volume-title":"Nat. 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