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Since Toll-like receptor 9 (TLR9) favors the elimination of autoreactive B cells in the periphery, we assessed TLR9 function in SLE by analyzing the responses of B cells and plasmacytoid dendritic cells (pDCs) isolated from healthy donors and patients after stimulation with CpG, a TLR9 agonist. We found that SLE B cells from patients without hydroxychloroquine treatment displayed defective in vitro TLR9 responses, as illustrated by the impaired upregulation of B cell activation molecules and the diminished production of various cytokines including antiinflammatory IL-10. In agreement with CD19 controlling TLR9 responses in B cells, decreased expression of the CD19\/CD21 complex on SLE B cells was detected as early as the transitional B cell stage. In contrast, TLR7 function was preserved in SLE B cells, whereas pDCs from SLE patients properly responded to TLR9 stimulation, thereby revealing that impaired TLR9 function in SLE was restricted to B cells. We conclude that abnormal CD19 expression and TLR9 tolerogenic function in SLE B cells may contribute to the break of B cell tolerance in these patients.<\/jats:p>","DOI":"10.1172\/jci.insight.96795","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:02:53Z","timestamp":1520420573000},"source":"Crossref","is-referenced-by-count":66,"title":["Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-8604","authenticated-orcid":true,"given":"Vincent","family":"Gies","sequence":"first","affiliation":[{"name":"CNRS UPR 3572 \u201cImmunopathology and Therapeutic Chemistry\u201d\/Laboratory of Excellence M\u00e9dalis, Institute of Molecular and Cellular Biology (IBMC), Strasbourg, France."},{"name":"Department of Clinical Immunology and Internal Medicine, National Reference Center for Rare Autoimmune Diseases, University Hospital, 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