{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:49:46Z","timestamp":1790858986724,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T00:00:00Z","timestamp":1482278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000032","name":"Institute of Infection and Immunity","doi-asserted-by":"publisher","award":["MOP\u201093771"],"award-info":[{"award-number":["MOP\u201093771"]}],"id":[{"id":"10.13039\/501100000032","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>Control of B\u2010cell signal transduction is critical to prevent production of pathological autoantibodies. Tandem PH domain containing proteins (TAPPs) specifically bind PI(3,4)P2, a phosphoinositide product generated by PI 3\u2010kinases and the phosphatase SHIP. TAPP KI mice bearing PH domain\u2010inactivating mutations in both TAPP1 and TAPP2 genes, uncoupling them from PI(3,4)P2, exhibit increased BCR\u2010induced activation of the kinase Akt and develop lupus\u2010like characteristics including anti\u2010DNA antibodies and deposition of immune complexes in kidneys. Here, we find that TAPP KI mice develop chronic germinal centers (GCs) with age and show abnormal expression of B\u2010cell activation and memory markers. Upon immunization with T\u2010dependent Ag, TAPP KI mice develop functional but abnormally large GCs, associated with increased GC B\u2010cell survival. Disruption of chronic GCs in TAPP KI mice by deletion of the costimulatory molecule ICOS abrogate anti\u2010DNA and anti\u2010nuclear antibody production in TAPP KI mice, indicating an essential role for GCs. Moreover, TAPP KI B cells are sufficient to drive chronic GC responses and recapitulate the autoimmune phenotype in BM chimeric mice. Our findings demonstrate a B\u2010cell\u2010intrinsic role of TAPP\u2013PI(3,4)P2 interaction in regulating GC responses and autoantibody production and suggest that uncontrolled Akt activity in B cells can drive autoimmunity.<\/jats:p>","DOI":"10.1002\/eji.201646596","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T12:36:18Z","timestamp":1479299778000},"page":"280-290","source":"Crossref","is-referenced-by-count":14,"title":["B\u2010cell\u2010intrinsic function of TAPP adaptors in controlling germinal center responses and autoantibody production in mice"],"prefix":"10.1002","volume":"47","author":[{"given":"Nipun","family":"Jayachandran","sequence":"first","affiliation":[{"name":"Department of Immunology University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Landego","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Manitoba  Winnipeg 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