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In this study, we showed that the class-switched IgG autoantibody response in MRL\/Faslpr\/lpr and C57\/Sle1Sle2Sle2 mice was blocked by the CID 1067700 compound, which specifically targeted Ras-related in brain 7 (Rab7), an endosome-localized small GTPase that was upregulated in activated human and mouse lupus B cells, leading to prevention of disease development and extension of lifespan. These were associated with decreased IgG-expressing B cells and plasma cells, but unchanged numbers and functions of myeloid cells and T cells. The Rab7 inhibitor suppressed T cell\u2013dependent and T cell\u2013independent Ab responses, but it did not affect T cell\u2013mediated clearance of Chlamydia infection, consistent with a B cell\u2013specific role of Rab7. Indeed, B cells and plasma cells were inherently sensitive to Rab7 gene knockout or Rab7 activity inhibition in class switching and survival, respectively, whereas proliferation\/survival of B cells and generation of plasma cells were not affected. Impairment of NF-\u03baB activation upon Rab7 inhibition, together with the rescue of B cell class switching and plasma cell survival by enforced NF-\u03baB activation, indicated that Rab7 mediates these processes by promoting NF-\u03baB activation, likely through signal transduction on intracellular membrane structures. Thus, a single Rab7-inhibiting small molecule can target two stages of B cell differentiation to dampen the pathogenic autoantibody response in lupus.<\/jats:p>","DOI":"10.4049\/jimmunol.1601427","type":"journal-article","created":{"date-parts":[[2016,10,15]],"date-time":"2016-10-15T01:49:56Z","timestamp":1476496196000},"page":"3792-3805","source":"Crossref","is-referenced-by-count":38,"title":["Small Molecule Inhibition of Rab7 Impairs B Cell Class Switching and Plasma Cell Survival To Dampen the Autoantibody Response in Murine Lupus"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-7234","authenticated-orcid":false,"given":"Tonika","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-7048","authenticated-orcid":false,"given":"Dennis V","family":"Kulp","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7549-0812","authenticated-orcid":false,"given":"Julia","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of 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