{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:16:45Z","timestamp":1791415005136,"version":"4.3.3"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IgD\u2212CD27\u2212 double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis (MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgD\u2212CD27+ class-switched memory (CSM) and IgD+CD27\u2212 naive B cells of HC (n = 48) and MS patients (n = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients (n = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. Phenotypic analysis indicated a mature state of DN B cells by low CD5, CD10, and CD38 expression. However, the frequency of CD95+ and IgA+ cells was lower in DN versus CSM B cells. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although &amp;gt;95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state.<\/jats:p>","DOI":"10.4049\/jimmunol.1801236","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T21:25:19Z","timestamp":1565213119000},"page":"1650-1664","source":"Crossref","is-referenced-by-count":49,"title":["Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD\u2212CD27\u2212 Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients"],"prefix":"10.1093","volume":"203","author":[{"given":"Judith","family":"Fraussen","sequence":"first","affiliation":[{"name":"Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg , 3500 Hasselt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Marquez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale 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,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-2739","authenticated-orcid":false,"given":"Chrysoula","family":"Zografou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06519"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van Wijmeersch","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg , 3500 Hasselt ,","place":["Belgium"]},{"name":"Rehabilitation and MS-Center , 3900 Pelt ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa M","family":"Villar","sequence":"additional","affiliation":[{"name":"Departamento de Inmunologia, Hospital Universitario Ram\u00f3n y Cajal , 28034 Madrid 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