{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:33:43Z","timestamp":1782894823828,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,2]],"date-time":"2019-02-02T00:00:00Z","timestamp":1549065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Anti\u2013citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA). Aside from autoantibody production, the function of autoantigen\u2010specific B cells remains poorly understood in the context of this disease. This study set out to elucidate autoantigen\u2010specific B cell functions through the isolation and immortalization of unique citrullinated protein\/peptide (CP)\u2013reactive B cell clones from RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>B cell clones from either the blood or synovial fluid of cyclic citrullinated peptide 2 (CCP2) antibody\u2013positive RA patients were immortalized by genetic reprogramming with Bcl\u20106 and Bcl\u2010xL. Enzyme\u2010linked immunosorbent assay and flow cytometry were used to identify CCP2\u2010reactive clones and to further characterize surface marker and cytokine expression as well as B cell receptor signaling competence. Global gene expression profiles were interrogated by RNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three unique CP\u2010reactive memory B cell clones were generated from the blood or synovial fluid of 2 RA patients. CP\u2010reactive memory B cells did not appear to be broadly cross\u2010reactive, but rather had a fairly restricted epitope recognition profile. These clones were able to secrete both pro\u2010 and antiinflammatory cytokines and had a unique surface profile of costimulatory molecules and receptors, including CD40 and C5a receptor type 1, when compared to non\u2010CP\u2013reactive clones from the same patient. In addition, CP\u2010reactive clones bound citrullinated protein, but not native protein, and could mobilize calcium in response to antigen binding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CP\u2010reactive memory B cells comprise a rare, seemingly oligoclonal population with restricted epitope specificity and distinct phenotypic and molecular characteristics suggestive of antigen\u2010presenting cells. Cloning by genetic reprogramming opens new avenues to study the function of autoreactive memory B cells, especially in terms of antigen processing, presentation, and subsequent T cell polarization.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40739","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T20:12:37Z","timestamp":1538424757000},"page":"340-350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Generation and Characterization of Anti\u2013Citrullinated Protein Antibody\u2013Producing B Cell Clones From Rheumatoid Arthritis Patients"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-6131","authenticated-orcid":false,"given":"Kristine","family":"Germar","sequence":"first","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Fehres","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans U.","family":"Scherer","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"van Uden","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Pollastro","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Yeremenko","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Hansson","sequence":"additional","affiliation":[{"name":"Karolinska Institutet\/Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla F.","family":"Kerkman","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen I. H.","family":"van der Voort","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Reed","sequence":"additional","affiliation":[{"name":"Karolinska Institutet\/Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Maassen","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Kwakkenbos","sequence":"additional","affiliation":[{"name":"AIMM Therapeutics and Academic Medical Center University of Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen Q.","family":"Bakker","sequence":"additional","affiliation":[{"name":"AIMM Therapeutics and Academic Medical Center University of Amsterdam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Klareskog","sequence":"additional","affiliation":[{"name":"Karolinska Institutet\/Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivianne","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Karolinska Institutet\/Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek","family":"de Vries","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 E. 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