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This study was undertaken to identify the B cell compartment from which these lymphoproliferations emerge and determine the mechanisms that promote clonal B cell expansion in patients with <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The reactivity of antibodies expressed by CD19+CD10\u2212CD27\u2212IgM+CD21<jats:sup>\u2212\/low<\/jats:sup> cells isolated from the blood of patients with SS was tested using a\u00a0polymerase chain reaction\u2013based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clonal expansions were identified in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>21<jats:sup>\u2212\/low<\/jats:sup> B cells isolated from the peripheral blood of 3 patients with <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>. These lymphoproliferations expressed B cell receptors (<jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>s) that displayed somatic hypermutation lineage trees characteristic of a strong selection by antigens; one of these antigens was identified as a ribosomal self antigen. When the mutated <jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content> sequences expressed by the expanded <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>21<jats:sup>\u2212\/low<\/jats:sup> B cell clones from patients with <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> were reverted in\u00a0vitro to their germline counterparts, one clone remained autoreactive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Clonal lymphoproliferations in patients with <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> preferentially accumulate in the autoreactive <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>21<jats:sup>\u2212\/low<\/jats:sup> B cell compartment often expanded in these subjects, and recognition of self antigens may drive the clonal B cell expansion while further refining <jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content> self\u2010reactivity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40352","type":"journal-article","created":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T15:42:35Z","timestamp":1509032555000},"page":"298-307","source":"Crossref","is-referenced-by-count":33,"title":["Accumulation of Antigen\u2010Driven Lymphoproliferations in Complement Receptor 2\/<scp>CD<\/scp>21<sup>\u2212\/low<\/sup> B Cells From Patients With Sj\u00f6gren's Syndrome"],"prefix":"10.1002","volume":"70","author":[{"given":"Salom\u00e9","family":"Glauzy","sequence":"first","affiliation":[{"name":"Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Boccitto","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Bannock","sequence":"additional","affiliation":[{"name":"Yale University School of 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