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This study was undertaken to characterize early B cell tolerance checkpoints in patients with SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an in vitro polymerase chain reaction\u2013based approach that allows the expression of recombinant antibodies cloned from single B cells, we tested the reactivity of antibodies expressed by 212 CD19+CD21<jats:sup>low<\/jats:sup>CD10+IgM<jats:sup>high<\/jats:sup>CD27\u2212 new emigrant\/transitional B cells and 190 CD19+CD21+CD10\u2212IgM+CD27\u2212 mature naive B cells from 10 patients with SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to serum from healthy donors, serum from patients with SSc displayed elevated proportions of polyreactive and antinuclear\u2010reactive new emigrant\/transitional B cells that recognize topoisomerase I, suggesting that defective central B cell tolerance contributes to the production of serum autoantibodies characteristic of the disease. Frequencies of autoreactive mature naive B cells were also significantly increased in SSc patients compared to healthy donors, thus indicating that a peripheral B cell tolerance checkpoint may be impaired in SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Defective counterselection of developing autoreactive naive B cells in SSc leads to the production of self antigen\u2013specific B cells that may secrete autoantibodies and allow the formation of immune complexes, which promote fibrosis in SSc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41927","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T05:27:02Z","timestamp":1626672422000},"page":"307-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of <scp>Self Antigen<\/scp>\u2013Specific 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