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Although the pathogenic relationship between systemic autoimmunity and the clinical manifestations remains unknown, <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients have immunological abnormalities including the production of disease\u2010specific autoantibodies. Recent studies have demonstrated that B cells play a crucial role in systemic autoimmunity and disease expression via various functions in addition to autoantibody production. Recent studies show that B cells from <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients demonstrate an upregulated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19 signaling pathway, which is a crucial regulator of B\u2010cell activation, that induces <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010specific autoantibody production in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. In addition, B cells from <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients exhibit an overexpression of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19. Consistently, in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19 transgenic mice, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19 overexpression induces <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c\u2010specific autoantibody production. <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients have also intrinsic B\u2010cell abnormalities characterized by chronic hyperreactivity of memory B cells, possibly due to <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19 overexpression. Similarly, B cells from a tight\u2010skin mouse, a genetic model of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c, show augmented <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19 signaling and chronic hyperreactivity. Furthermore, in bleomycin\u2010induced <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c model mice, endogenous ligands for Toll\u2010like receptors, induced by bleomycin treatment, stimulate B cells to produce various fibrogenic cytokines and autoantibodies. Remarkably, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19 loss results in inhibition of B\u2010cell hyperreactivity and elimination of autoantibody production, which is associated with improvement of fibrosis. Taken together, altered B\u2010cell function may result in tissue fibrosis, as well as autoimmunity, in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. Although further studies and greater understanding are needed, B cells are potential therapeutic target in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c.<\/jats:p>","DOI":"10.1111\/1346-8138.13184","type":"journal-article","created":{"date-parts":[[2016,1,5]],"date-time":"2016-01-05T17:54:13Z","timestamp":1452016453000},"page":"39-45","source":"Crossref","is-referenced-by-count":30,"title":["B lymphocytes in systemic sclerosis: Abnormalities and therapeutic targets"],"prefix":"10.1111","volume":"43","author":[{"given":"Ayumi","family":"Yoshizaki","sequence":"first","affiliation":[{"name":"Department of Dermatology The University of Tokyo Graduate School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,4]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets and 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