{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:18:35Z","timestamp":1793056715878,"version":"4.5.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NWO gravitation program \u201cInstitute for Chemical Immunology\u201d","award":["NWO-024.002.009"],"award-info":[{"award-number":["NWO-024.002.009"]}]},{"name":"IMI funded project RTCure","award":["777357"],"award-info":[{"award-number":["777357"]}]},{"name":"Target to B!","award":["LSHM18055-5GF"],"award-info":[{"award-number":["LSHM18055-5GF"]}]},{"name":"European Research Council","award":["AdG2019-884796"],"award-info":[{"award-number":["AdG2019-884796"]}]},{"name":"NWO-ZonMW VIDI grant","award":["09150172010067"],"award-info":[{"award-number":["09150172010067"]}]},{"name":"NWO-ZonMW OffRoad Grant","award":["451001012"],"award-info":[{"award-number":["451001012"]}]},{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"crossref","award":["17-1-402,LLP5,15-2-402,18-1-205"],"award-info":[{"award-number":["17-1-402,LLP5,15-2-402,18-1-205"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,23]]},"abstract":"<jats:p>Many autoimmune diseases (AIDs) are characterized by the persistence of autoreactive B cell responses, which have been directly implicated in disease pathogenesis. How and why these cells are generated or how they are maintained for years is largely unknown. Rheumatoid arthritis (RA) is among the most common AIDs and is characterized by autoantibodies recognizing proteins with posttranslational modifications (PTMs). This PTM-directed autoreactive B cell compartment is ill defined. Here, we visualized the B cell response against the three main types of PTM antigens implicated in RA by spectral flow cytometry. Our results showed extensive cross-reactivity of PTM-directed B cells against all three PTM antigens (citrulline, homocitrulline, and acetyllysine). Unsupervised clustering revealed several distinct memory B cell (mBC) populations. PTM-directed cells clustered with the most recently activated class-switched mBC phenotype, with high CD80, low CD24, and low CD21 expression. Notably, patients also harbored large fractions of PTM-directed plasmablasts (PBs). Both PTM-directed mBCs and PBs showed high expression of CXCR3, a receptor for chemokines present in abundance in arthritic joints. Together, our data provide detailed insight into the biology of B cell autoreactivity and its remarkable, seemingly exhaustless persistence in a prominent human AID.<\/jats:p>","DOI":"10.1172\/jci.insight.172006","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T12:10:18Z","timestamp":1695125418000},"source":"Crossref","is-referenced-by-count":49,"title":["Autoreactive B cells in rheumatoid arthritis include mainly activated CXCR3+ memory B cells and plasmablasts"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-4256","authenticated-orcid":true,"given":"Sanne","family":"Reijm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanneke C.","family":"Kwekkeboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nienke J.","family":"Blomberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-8925","authenticated-orcid":true,"given":"Jolien","family":"Suurmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"van der Woude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 E.M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans U.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032534"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30070-3"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02017-5"},{"key":"B4","unstructured":"Young C, McGill SC. 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