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To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21<jats:sup>\u2212\/low<\/jats:sup> B cells). In this study, we sought to determine whether there was any correlation between CD21<jats:sup>\u2212\/low<\/jats:sup> B cells and clinical outcome in patients with established RA, either ACPA<jats:sup>+<\/jats:sup>\/RF<jats:sup>+<\/jats:sup> (n\u00a0=\u00a027) or ACPA<jats:sup>\u2212<\/jats:sup>\/RF<jats:sup>\u2212<\/jats:sup> (n\u00a0=\u00a010). Healthy donors (n\u00a0=\u00a017) were included as controls. The proportion of the CD21<jats:sup>\u2212\/low<\/jats:sup> CD27<jats:sup>\u2212<\/jats:sup>IgD<jats:sup>\u2212<\/jats:sup> memory B cell subset in peripheral blood (PB) was significantly increased in ACPA<jats:sup>+<\/jats:sup>\/RF<jats:sup>+<\/jats:sup> RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.57, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.04). The levels of the chemokines CXCL\u20109 and CXCL\u201010 were higher in synovial fluid than in plasma, and PB CD21<jats:sup>\u2212\/low<\/jats:sup> cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21<jats:sup>\u2212\/low<\/jats:sup>, approximately 40% of that population was CD27<jats:sup>\u2212<\/jats:sup>IgD<jats:sup>\u2212<\/jats:sup>, and a third of those expressed the pro\u2010osteoclastogenic factor receptor activator of the nuclear factor \u03baB ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL\u20106, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27<jats:sup>\u2212<\/jats:sup>IgD<jats:sup>\u2212<\/jats:sup> subset of CD21<jats:sup>\u2212\/low<\/jats:sup> B cells may mediate joint destruction in patients with ACPA<jats:sup>+<\/jats:sup>\/RF<jats:sup>+<\/jats:sup> RA.<\/jats:p>","DOI":"10.1111\/sji.12792","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T12:52:42Z","timestamp":1559134362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["CD21<sup>\u2212\/low<\/sup> B cells associate with joint damage in rheumatoid arthritis patients"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2708-1990","authenticated-orcid":false,"given":"Katrin","family":"Thorarinsdottir","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Inflammation Research University of Gothenburg Gothenburg 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