{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:04:30Z","timestamp":1770095070497,"version":"3.49.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2004,6,1]],"date-time":"2004-06-01T00:00:00Z","timestamp":1086048000000},"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":[[2004,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Little is known about the pathogenic mechanisms of IgA nephropathy, despite being the most prevalent form of glomerulonephritis in humans. We report in this study that in (New Zealand White (NZW) \u00d7 C57BL\/6)F1 mice predisposed to autoimmune diseases, the expression of a human bcl-2 (hbcl-2) transgene in B cells promotes a CD4-dependent lupus-like syndrome characterized by IgG and IgA hypergammaglobulinemia, autoantibody production, and the development of a fatal glomerulonephritis. Histopathological analysis of glomerular lesions reveals that the glomerulonephritis observed in these animals resembles that of human IgA nephropathy. The overexpression of Bcl-2 in B cells selectively enhances systemic IgA immune responses to T-dependent Ags. Significantly, serum IgA purified from (NZW \u00d7 C57BL\/6)F1-hbcl-2 transgenic mice, but not from nontransgenic littermates, shows reduced levels of galactosylation and sialylation and an increased ability to deposit in the glomeruli, as observed in human patients with IgA nephropathy. Our results indicate that defects in the regulation of B lymphocyte survival associated with aberrant IgA glycosylation may be critically involved in the pathogenesis of IgA nephropathy, and that (NZW \u00d7 C57BL\/6)F1-hbcl-2 Tg mice provide a new experimental model for this form of glomerulonephritis.<\/jats:p>","DOI":"10.4049\/jimmunol.172.11.7177","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:55:42Z","timestamp":1398030942000},"page":"7177-7185","source":"Crossref","is-referenced-by-count":40,"title":["Inhibition of B Cell Death Causes the Development of an IgA Nephropathy in (New Zealand White \u00d7 C57BL\/6)F1-\n                    <i>bcl-2<\/i>\n                    Transgenic Mice"],"prefix":"10.1093","volume":"172","author":[{"given":"Regina","family":"Marquina","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, Department of Molecular Biology, Unit Associated with Centro de Investigaciones Biologicas\/Consejo Superior de Investigaciones Cientificas, University of Cantabria , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A","family":"Di\u0301ez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Department of Molecular Biology, Unit Associated with Centro de Investigaciones Biologicas\/Consejo Superior de Investigaciones Cientificas, University of Cantabria , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Lo\u0301pez-Hoyos","sequence":"additional","affiliation":[{"name":"Immunology, Hospital Universitario Marque\u0301s de Valdecilla , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Buelta","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgery Sciences, University of Cantabria , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Kuroki","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva , Geneva ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva , Geneva ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Villegas","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cellular Biology, University of Cantabria , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pihlgren","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva , Geneva ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire-Anne","family":"Siegrist","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva , Geneva ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Arias","sequence":"additional","affiliation":[{"name":"Nephrology, Hospital Universitario Marque\u0301s de Valdecilla , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shozo","family":"Izui","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Geneva , Geneva ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesu\u0301s","family":"Merino","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Department of Molecular Biology, Unit Associated with Centro de Investigaciones Biologicas\/Consejo Superior de Investigaciones Cientificas, University of Cantabria , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramo\u0301n","family":"Merino","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Department of Molecular Biology, Unit Associated with Centro de Investigaciones Biologicas\/Consejo Superior de Investigaciones Cientificas, University of Cantabria , Santander ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,6,1]]},"reference":[{"key":"2026020211302811800_R1","first-page":"738","volume-title":"N. 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