{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:03:11Z","timestamp":1770717791478,"version":"3.49.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,10,1]]},"abstract":"<jats:p>Males from the BXSB murine strain (H-2b) spontaneously develop an autoimmune syndrome with features of systemic lupus erythematosus (SLE), which results in part from the action of a mutant gene (Yaa) located on the Y chromosome. Like other H-2b mice, the BXSB strain does not express the class II major histocompatibility complex antigen, I-E. Here we report that the expression of I-E (E alpha dE beta b) in BXSB males bearing an E alpha d transgene prevents hypergammaglobulinemia, autoantibody production, and subsequent autoimmune glomerulonephritis. These transgenic mice bear on the majority of their B cells not only I-E molecules, but also an I-E alpha chain-derived peptide presented by a higher number of I-Ab molecules, as recognized by the Y-Ae monoclonal antibody. The I-E+ B cells appear less activated in vivo than the I-E- B cells, a minor population. This limited activation of the I-E+ B cells does not reflect a functional deficiency of this cell population, since it can be stimulated to IgM production in vitro by lipopolysaccharides at an even higher level than the I-E- B cell population. The development of the autoimmune syndrome in the transgenic and nontransgenic bone marrow chimeric mice argues against the possibility that the induction of regulatory T cells or clonal deletion of potential autoreactive T cells as a result of I-E expression is a mechanism of the protection conferred by the E alpha d transgene. We propose a novel mechanism by which the E alpha d transgene protects BXSB mice against SLE: overexpression of I-E alpha chains results in the generation of excessive amounts of a peptide displaying a high affinity to the I-Ab molecule, thereby competing with pathogenic autoantigen-derived peptides for presentation by B lymphocytes and preventing their excessive stimulation.<\/jats:p>","DOI":"10.1084\/jem.178.4.1189","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1189-1197","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E alpha chain."],"prefix":"10.1084","volume":"178","author":[{"given":"R","family":"Merino","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Fossati","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Muniesa","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Huarte","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J D","family":"Vassalli","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Izui","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1993,10,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/178\/4\/1189\/1674771\/1189.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/178\/4\/1189\/1674771\/1189.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T05:02:13Z","timestamp":1690261333000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/178\/4\/1189\/24950\/Prevention-of-systemic-lupus-erythematosus-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,10,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1993,10,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.178.4.1189","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,10,1]]}}}