{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:39:55Z","timestamp":1762864795099},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,6,1]]},"abstract":"<jats:p>The bcl-2 protooncogene has been shown to provide a survival signal to self-reactive B cells, but it fails to override their developmental arrest after encounter with antigen. Furthermore, constitutive expression of bcl-2 in B cells does not promote the development of autoimmune disease in most strains of mice, indicating that signals other than those conferred by bcl-2 are required for long-term survival and differentiation of self-reactive B cells in vivo. To further examine the factors that are required for the pathogenesis of autoimmune disease, we have assessed the effect of bcl-2 overexpression on the development of host-versus-graft disease, a self-limited model of systemic autoimmune disease. In this model, injection of spleen cells from (C57BL\/6 x BALB\/c)F1 hybrid mice into BALB\/c newborn parental mice induces immunological tolerance to donor tissues and activation of autoreactive F1 donor B cells through interactions provided by allogeneic host CD4+ T cells. BALB\/c newborns injected with spleen cells from (C57BL\/6 x BALB\/c)F1 mice expressing a bcl-2 transgene in B cells developed high levels of anti-single-stranded DNA and a wide range of pathogenic autoantibodies that were not or barely detectable in mice injected with nontransgenic spleen cells. In mice injected with transgenic B cells, the levels of pathogenic autoantibodies remained high during the course of the study and were associated with long-term persistence of donor B cells, development of a severe autoimmune disease, and accelerated mortality. These results demonstrate that bcl-2 can provide survival signals for the maintenance and differentiation of autoreactive B cells, and suggest that both increased B cell survival and T cell help play critical roles in the development of certain forms of systemic autoimmune disease.<\/jats:p>","DOI":"10.1084\/jem.183.6.2523","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"2523-2531","update-policy":"http:\/\/dx.doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Constitutive expression of bcl-2 in B cells causes a lethal form of lupuslike autoimmune disease after induction of neonatal tolerance to H-2b alloantigens."],"prefix":"10.1084","volume":"183","author":[{"given":"M","family":"L\u00f3pez-Hoyos","sequence":"first","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Carri\u00f3","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Merino","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Buelta","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Izui","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Merino","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitar\u00eco M. Valdecilla, Santander, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1996,6,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/6\/2523\/1678378\/2523.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/6\/2523\/1678378\/2523.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:11:52Z","timestamp":1690269112000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/183\/6\/2523\/21419\/Constitutive-expression-of-bcl-2-in-B-cells-causes"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1996,6,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.183.6.2523","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,6,1]]}}}