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The aim of this study was to determine the functional role of normal pre-na\u00efve B cells during immune responses and possible abnormalities in systemic lupus erythematosus (SLE) that might contribute to disease pathogenesis.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Pre-na\u00efve, na\u00efve, and memory B cells from healthy individuals and SLE patients were stimulated through CD40 and were analyzed for interleukin-10 (IL-10) production and co-stimulatory molecule expression and their regulation of T-cell activation. Autoreactivity of antibodies produced by pre-na\u00efve B cells was tested by measuring immunoglobulin M (IgM) autoantibodies in culture supernatants after differentiation.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>CD40-stimulated pre-na\u00efve B cells produce larger amounts of IL-10 but did not suppress CD4<jats:sup>+<\/jats:sup> T-cell cytokine production. Activated pre-na\u00efve B cells demonstrated IL-10-mediated ineffective promotion of CD4<jats:sup>+<\/jats:sup> T-cell proliferation and induction of CD4<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> T cells and IL-10 independent impairment of co-stimulatory molecule expression and tumor necrosis factor-alpha (TNF-\u03b1) and IL-6 production. IgM antibodies produced by differentiated pre-na\u00efve B cells were reactive to single-stranded deoxyribonucleic acid. SLE pre-na\u00efve B cells were defective in producing IL-10, and co-stimulatory molecule expression was enhanced, resulting in promotion of robust CD4<jats:sup>+<\/jats:sup> T-cell proliferation.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>There is an inherent and IL-10-mediated mechanism that limits the capacity of normal pre-na\u00efve B cells from participating in cellular immune response, but these cells can differentiate into autoantibody-secreting plasma cells. In SLE, defects in IL-10 secretion permit pre-na\u00efve B cells to promote CD4<jats:sup>+<\/jats:sup> T-cell activation and may thereby enhance the development of autoimmunity.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/s13075-015-0687-1","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T15:34:24Z","timestamp":1437752064000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Autoregulatory function of interleukin-10-producing pre-na\u00efve B cells is defective in systemic lupus erythematosus"],"prefix":"10.1186","volume":"17","author":[{"given":"Ji Hyun","family":"Sim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang-Rae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soog-Hee","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Je","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Lipsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisoo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,25]]},"reference":[{"key":"687_CR1","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/nature03724","volume":"435","author":"CC Goodnow","year":"2005","unstructured":"Goodnow CC, Sprent J, de St F, Groth B, Vinuesa CG. 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