{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:24:01Z","timestamp":1779179041824,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR072212"],"award-info":[{"award-number":["R01 AR072212"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007820","name":"Alliance for Lupus Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"Objective<\/jats:title>To determine whether systemic lupus erythematosus (SLE<\/jats:styled-content>) can develop in the absence of BAFF<\/jats:styled-content> in an SLE<\/jats:styled-content>\u2010prone host.<\/jats:p><\/jats:sec>Methods<\/jats:title>Starting with C57BL<\/jats:styled-content>\/6 mice that express a human BCL<\/jats:styled-content>2<\/jats:italic> transgene (Tg) in their B cells (thereby rendering B cell survival largely independent of BAFF<\/jats:styled-content>\u2010triggered signals), we introgressed this Tg into NZM<\/jats:styled-content> 2328 mice genetically deficient in BAFF<\/jats:styled-content> (NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) to generate NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>.Bcl2<\/jats:italic>Tg<\/jats:italic><\/jats:sup> mice. Expression of human Bcl\u20102 and lymphocyte profiles were assessed by fluorescence\u2010activated cell sorting, and serologic profiles were determined by enzyme\u2010linked immunosorbent assay. Immunofluorescence and histologic analyses were performed to assess renal immunopathologic features in the mice, and clinical disease was assessed according to the outcomes of severe proteinuria and death.<\/jats:p><\/jats:sec>Results<\/jats:title>In comparison to their non\u2010Tg NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> littermates (n \u2265 7), NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>.Bcl2<\/jats:italic>Tg<\/jats:italic><\/jats:sup> mice (n \u2265 8) overexpressed Bcl\u20102 in their B cells and developed significantly increased percentages and numbers of B cells and plasma cells, serum levels of IgG autoantibodies, glomerular deposition of IgG and C3, and severity of glomerular and tubulointerstitial inflammation, culminating in severe proteinuria and death (all P<\/jats:italic> < 0.05 versus NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> littermates). The time course for development of SLE<\/jats:styled-content>\u2010like features in NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>.Bcl2<\/jats:italic>Tg<\/jats:italic><\/jats:sup> mice was more rapid than has been previously observed in NZM<\/jats:styled-content> 2328 wild\u2010type mice (median age at death 4.5 months versus 7.5 months). NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>.Bcl2<\/jats:italic>Tg<\/jats:italic><\/jats:sup> mice remained responsive to BAFF<\/jats:styled-content>, since reintroduction of the Baff<\/jats:italic> gene into these mice further accelerated the course of disease (median age at death 3 months).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The role of BAFF<\/jats:styled-content> in the development of SLE<\/jats:styled-content>\u2010like disease may be dispensable as long as B cell survival is preserved via a BAFF<\/jats:styled-content>\u2010independent pathway. This may help explain the limited and variable clinical success with BAFF<\/jats:styled-content> antagonists in human SLE<\/jats:styled-content>. Thus, NZM<\/jats:styled-content>.Baff<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>.Bcl2<\/jats:italic>Tg<\/jats:italic><\/jats:sup> mice may serve as a powerful murine model for the study of BAFF<\/jats:styled-content>\u2010independent SLE<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41097","type":"journal-article","created":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T14:25:00Z","timestamp":1567866300000},"page":"292-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Development of Murine Systemic Lupus Erythematosus in the Absence of BAFF<\/scp>"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8272-7873","authenticated-orcid":false,"given":"William","family":"Stohl","sequence":"first","affiliation":[{"name":"University of Southern California Keck School of Medicine Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Yu","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Chalmers","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaim","family":"Putterman","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaim O.","family":"Jacob","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.4.1295"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000466"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.1.129"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.953"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200207)32:7<2004::AID-IMMU2004>3.0.CO;2-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni829"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00183-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061964"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35010115"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26385"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.4.2671"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34400"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-205144"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23047"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207653"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207654"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61354-2"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30613"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40049"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211631"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-205067"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2076"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24699"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324692"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2245"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.19.8661"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900098"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-280"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2001.5079"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33458"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.11.1697"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1428"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1451"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004142"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.793"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802948"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39210"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40141"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39744"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203317719334"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3351"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27515"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38907"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27233"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34359"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38037"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.2.435.435"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.7.1147"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.138"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061965"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7394"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-017319"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.07.009"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.41097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.41097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:44:43Z","timestamp":1759927483000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.41097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1002\/art.41097"],"URL":"https:\/\/doi.org\/10.1002\/art.41097","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]},"assertion":[{"value":"2019-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}