{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:12:20Z","timestamp":1791162740422,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"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":[[2006,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lat Y136F knock-in mice harbor a point mutation in Tyr136 of the linker for activation of T cells and show accumulation of Th2 effector cells and IgG1 and IgE hypergammaglobulinemia. B cell activation is not a direct effect of the mutation on B cells since in the absence of T cells, mutant B cells do not show an activated phenotype. After adoptive transfer of linker for activation of T cell mutant T cells into wild-type, T cell-deficient recipients, recipient B cells become activated. We show in vivo and in vitro that the LatY136F mutation promotes T cell-dependent B cell activation leading to germinal center, memory, and plasma cell formation even in an MHC class II-independent manner. All the plasma and memory B cell populations found in physiological T cell-dependent B cell responses are found. Characterization of the abundant plasmablasts found in secondary lymphoid organs of LatY136F mice revealed the presence of a previously uncharacterized CD93-expressing subpopulation, whose presence was confirmed in wild-type mice after immunization. In LatY136F mice, B cell activation was polyclonal and not Ag-driven because the increase in serum IgG1 and IgE concentrations involved Abs and autoantibodies with different specificities equally. Although the noncomplement-fixing IgG1 and IgE are the only isotypes significantly increased in LatY136F serum, we observed early-onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and severe proteinuria. These results show that Th2 cells developing in LatY136F mice can trigger polyclonal B cell activation and thereby lead to systemic autoimmune disease.<\/jats:p>","DOI":"10.4049\/jimmunol.177.4.2285","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:20:43Z","timestamp":1397848843000},"page":"2285-2293","source":"Crossref","is-referenced-by-count":44,"title":["The Th2 Lymphoproliferation Developing in\n                    <i>Lat<\/i>\n                    <i>Y136F<\/i>\n                    Mutant Mice Triggers Polyclonal B Cell Activation and Systemic Autoimmunity"],"prefix":"10.1093","volume":"177","author":[{"given":"Ce\u0301line","family":"Genton","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Lausanne , Epalinges ,","place":["Switzerland"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Universite\u0301 de la Me\u0301dite\u0301rrane\u0301e , Marseille ,","place":["France"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozo","family":"Izui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, University of Geneva , Geneva ,","place":["Switzerland"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Malissen","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Universite\u0301 de la Me\u0301dite\u0301rrane\u0301e , Marseille ,","place":["France"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Delsol","sequence":"additional","affiliation":[{"name":"INSERM Unite\u0301 563, Centre de Physiopathologie de Toulouse-Purpa , Toulouse, F-31300 \u00a0","place":["France"]},{"name":"De\u0301partement Oncoge\u0301ne\u0300se et Signalisation dans les Cellules He\u0301matopoie\u0301tiques, Institut Fe\u0301de\u0301ratif de Recherche 30 and Laboratoire d\u2019Anatomie Pathologique, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert J","family":"Fournie\u0301","sequence":"additional","affiliation":[{"name":"INSERM Unite\u0301 563, Centre de Physiopathologie de Toulouse-Purpan , Toulouse, F-31300 \u00a0","place":["France"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Malissen","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Universite\u0301 de la Me\u0301dite\u0301rrane\u0301e , Marseille ,","place":["France"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Acha-Orbea","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Lausanne , Epalinges ,","place":["Switzerland"]},{"name":"De\u0301partement de Ge\u0301ne\u0301tique Fonctionnelle des Maladies des E\u0301pithe\u0301liums, Institut Fe\u0301de\u0301ratif de Recherche 30, Purpan\u2019s Hospital , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,8,15]]},"reference":[{"key":"2026020209055037000_R1","first-page":"787","volume-title":"Curr. Opin. Immunol.","year":"2004"},{"key":"2026020209055037000_R2","first-page":"397","volume-title":"Immunity","year":"2001"},{"key":"2026020209055037000_R3","first-page":"363","volume-title":"Springer Semin. Immunopathol.","year":"2003"},{"key":"2026020209055037000_R4","first-page":"2883","volume-title":"J. Immunol.","year":"1987"},{"key":"2026020209055037000_R5","first-page":"1221","volume-title":"Eur. J. Immunol.","year":"2001"},{"key":"2026020209055037000_R6","first-page":"3370","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026020209055037000_R7","first-page":"805","volume-title":"Nature","year":"1987"},{"key":"2026020209055037000_R8","first-page":"1755","volume-title":"J. Exp. Med.","year":"1987"},{"key":"2026020209055037000_R9","first-page":"245","volume-title":"Nature","year":"1998"},{"key":"2026020209055037000_R10","first-page":"341","volume-title":"Immunity","year":"2004"},{"key":"2026020209055037000_R11","first-page":"96","volume-title":"Science","year":"1998"},{"key":"2026020209055037000_R12","first-page":"e150","volume-title":"PLoS Biol.","year":"2005"},{"key":"2026020209055037000_R13","first-page":"487","volume-title":"Annu. Rev. Immunol.","year":"2005"},{"key":"2026020209055037000_R14","first-page":"53","volume-title":"Immunol. Rev.","year":"1997"},{"key":"2026020209055037000_R15","first-page":"885","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209055037000_R16","first-page":"111","volume-title":"J. Immunol.","year":"1937"},{"key":"2026020209055037000_R17","first-page":"343","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026020209055037000_R18","first-page":"537","volume-title":"Nature","year":"1985"},{"key":"2026020209055037000_R19","first-page":"1","volume-title":"Adv. Immunol.","year":"2005"},{"key":"2026020209055037000_R20","first-page":"2036","volume-title":"Science","year":"2002"},{"key":"2026020209055037000_R21","first-page":"2040","volume-title":"Science","year":"2002"},{"key":"2026020209055037000_R22","first-page":"4641","volume-title":"EMBO J.","year":"1995"},{"key":"2026020209055037000_R23","first-page":"1051","volume-title":"Cell","year":"1991"},{"key":"2026020209055037000_R24","first-page":"1577","volume-title":"Am. J. Pathol.","year":"1997"},{"key":"2026020209055037000_R25","first-page":"651","volume-title":"Int. J. Cancer","year":"1993"},{"key":"2026020209055037000_R26","first-page":"741","volume-title":"J. Histochem. Cytochem.","year":"1991"},{"key":"2026020209055037000_R27","first-page":"435","volume-title":"Immunity","year":"2001"},{"key":"2026020209055037000_R28","first-page":"4420","volume-title":"J. Immunol.","year":"1986"},{"key":"2026020209055037000_R29","first-page":"1689","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026020209055037000_R30","first-page":"911","volume-title":"Eur. J. Immunol.","year":"1988"},{"key":"2026020209055037000_R31","first-page":"351","volume-title":"Immunology","year":"2003"},{"key":"2026020209055037000_R32","first-page":"295","volume-title":"Immunity","year":"2003"},{"key":"2026020209055037000_R33","first-page":"4455","volume-title":"Mol. Cell. Biol.","year":"2005"},{"key":"2026020209055037000_R34","first-page":"1125","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026020209055037000_R35","first-page":"2025","volume-title":"J. Immunol.","year":"1990"},{"key":"2026020209055037000_R36","first-page":"1118","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020209055037000_R37","first-page":"1089","volume-title":"Eur. J. Immunol.","year":"1988"},{"key":"2026020209055037000_R38","first-page":"1597","volume-title":"J. Clin. Invest.","year":"1996"},{"key":"2026020209055037000_R39","first-page":"65","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020209055037000_R40","first-page":"2494","volume-title":"J. Am. Soc. Nephrol.","year":"2003"},{"key":"2026020209055037000_R41","first-page":"487","volume-title":"Annu. Rev. Immunol.","year":"1994"},{"key":"2026020209055037000_R42","first-page":"41","volume-title":"Immunity","year":"2005"},{"key":"2026020209055037000_R43","first-page":"451","volume-title":"Immunity","year":"1999"},{"key":"2026020209055037000_R44","first-page":"454","volume-title":"Nature","year":"2003"},{"key":"2026020209055037000_R45","first-page":"452","volume-title":"Nature","year":"2005"},{"key":"2026020209055037000_R46","first-page":"451","volume-title":"Immunity.","year":"2005"},{"key":"2026020209055037000_R47","first-page":"1326","volume-title":"Rheumatology","year":"2004"},{"key":"2026020209055037000_R48","first-page":"1762","volume-title":"J. Clin. Invest.","year":"1996"},{"key":"2026020209055037000_R49","first-page":"1198","volume-title":"J. Exp. Med.","year":"1978"},{"key":"2026020209055037000_R50","first-page":"169","volume-title":"Rom. J. Intern. Med.","year":"1992"},{"key":"2026020209055037000_R51","first-page":"946","volume-title":"Ann. Rheum. Dis.","year":"1989"},{"key":"2026020209055037000_R52","first-page":"229","volume-title":"Am. J. Pathol.","year":"1987"},{"key":"2026020209055037000_R53","first-page":"124","volume-title":"Clin. Exp. Immunol.","year":"1989"},{"key":"2026020209055037000_R54","first-page":"1699","volume-title":"J. Immunol.","year":"1983"},{"key":"2026020209055037000_R55","first-page":"1146","volume-title":"Arthritis Rheum.","year":"1985"},{"key":"2026020209055037000_R56","first-page":"3053","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020209055037000_R57","first-page":"140","volume-title":"Ann. NY Acad. Sci.","year":"2003"},{"key":"2026020209055037000_R58","first-page":"1497","volume-title":"Braz J. Med. Biol. Res.","year":"2004"},{"key":"2026020209055037000_R59","first-page":"679","volume-title":"Arch. Intern. Med.","year":"1981"},{"key":"2026020209055037000_R60","first-page":"941","volume-title":"Am. J. Kidney Dis.","year":"2000"},{"key":"2026020209055037000_R61","first-page":"34","volume-title":"Ann. Clin. Lab. Sci.","year":"1988"},{"key":"2026020209055037000_R62","first-page":"256","volume-title":"Nephron","year":"1976"},{"key":"2026020209055037000_R63","first-page":"31","volume-title":"Am. J. Nephrol.","year":"1981"},{"key":"2026020209055037000_R64","first-page":"128","volume-title":"Am. J. Trop. Med. Hyg.","year":"2000"},{"key":"2026020209055037000_R65","first-page":"310","volume-title":"Clin. Exp. Immunol.","year":"1982"},{"key":"2026020209055037000_R66","first-page":"3006","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020209055037000_R67","first-page":"333","volume-title":"Clin. Rheumatol.","year":"2003"},{"key":"2026020209055037000_R68","first-page":"343","volume-title":"J. Clin. Lab. Immunol.","year":"1979"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/177\/4\/2285\/62643226\/zim01606002285.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/177\/4\/2285\/62643226\/zim01606002285.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:07:24Z","timestamp":1770041244000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/177\/4\/2285\/8025160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8]]},"references-count":68,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2006,8,15]]},"published-print":{"date-parts":[[2006,8,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.177.4.2285","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,8]]},"published":{"date-parts":[[2006,8]]}}}