{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:16:21Z","timestamp":1791216981892,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"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":[[2012,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoantibodies against citrullinated protein Ags (ACPA) are associated with the development of rheumatoid arthritis (RA). This immune response against citrullinated protein Ags, which is thought to be facilitated by certain MHC HLA-DR alleles, is highly specific for this disease and has been speculated to be involved in the pathogenesis. We have previously studied cultures of B cells for the production of Abs against HLA Ags. The aim of the current study was to examine the role of B cells in the production of ACPA in patients with RA. Peripheral blood B cells from RA patients and healthy people were cultured with EL4-B5, a murine cell line expressing human CD40L, and with T cell factors to stimulate the in vitro production of Abs by B cells isolated from peripheral blood. ACPA were produced by cultured B cells from RA patients, as determined by reactivity to cyclic citrullinated peptide (CCP). The results showed that 22% of the healthy persons tested also had B cells that could produce ACPA. Patients with HLA-DR alleles carrying the RA-associated shared epitope appeared to have more B cells with autoimmune potential for CCP than those without such HLA alleles (odds ratio 8.1, p = 0.001). In healthy individuals, anti-CCP\u2013producing B cells were also observed more frequently if the RA-associated MHC genes were present (odds ratio 8.0, p = 0.01). Analysis of B cells in cultures may shed light on the interaction of genetic and environmental factors in the development of RA.<\/jats:p>","DOI":"10.4049\/jimmunol.1100577","type":"journal-article","created":{"date-parts":[[2012,2,16]],"date-time":"2012-02-16T05:40:48Z","timestamp":1329370848000},"page":"3542-3550","source":"Crossref","is-referenced-by-count":25,"title":["Production of Autoantibodies against Citrullinated Antigens\/Peptides by Human B Cells"],"prefix":"10.1093","volume":"188","author":[{"given":"Maria F","family":"Bellatin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Fallena","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donglan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Branch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Karp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Stastny","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,4,1]]},"reference":[{"key":"2025032409594626600_r1","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1136\/ard.2003.016808","article-title":"Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)","volume":"63","author":"Kastbom","year":"2004","journal-title":"Ann. 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Dis."},{"key":"2025032409594626600_r4","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/rheumatology\/kei203","article-title":"Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome","volume":"45","author":"Quinn","year":"2006","journal-title":"Rheumatology"},{"key":"2025032409594626600_r5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3","article-title":"The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide","volume":"43","author":"Schellekens","year":"2000","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/ar395","article-title":"Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value","volume":"4","author":"van Boekel","year":"2002","journal-title":"Arthritis Res."},{"key":"2025032409594626600_r7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/art.21629","article-title":"Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti-citrullinated protein antibodies in rheumatoid arthritis","volume":"54","author":"Pratesi","year":"2006","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r8","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1172\/JCI1316","article-title":"Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies","volume":"101","author":"Schellekens","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2025032409594626600_r9","first-page":"2535","article-title":"Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis","volume":"30","author":"Saraux","year":"2003","journal-title":"J. Rheumatol."},{"key":"2025032409594626600_r10","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1002\/art.11223","article-title":"Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis","volume":"48","author":"Rantap\u00e4\u00e4-Dahlqvist","year":"2003","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r11","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1002\/art.23618","article-title":"Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis","volume":"58","author":"Kinloch","year":"2008","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r12","doi-asserted-by":"crossref","first-page":"R94","DOI":"10.1186\/ar2478","article-title":"Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis","volume":"10","author":"Zhao","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"2025032409594626600_r13","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1002\/art.20316","article-title":"Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis","volume":"50","author":"van Gaalen","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/art.21575","article-title":"A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination","volume":"54","author":"Klareskog","year":"2006","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r15","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/art.22703","article-title":"Interaction between smoking, the shared epitope, and anti-cyclic citrullinated peptide: a mixed picture in three large North American rheumatoid arthritis cohorts","volume":"56","author":"Lee","year":"2007","journal-title":"Arthritis Rheum."},{"key":"2025032409594626600_r16","doi-asserted-by":"crossref","first-page":"538","DOI":"10.4049\/jimmunol.171.2.538","article-title":"Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule","volume":"171","author":"Hill","year":"2003","journal-title":"J. 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