{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:10:08Z","timestamp":1760267408246,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR-053483","GM-104938","AI-101934","AI-082741","AI-090343","AI-044215"],"award-info":[{"award-number":["AR-053483","GM-104938","AI-101934","AI-082741","AI-090343","AI-044215"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Earlier studies showed that the DNA-binding protein, Bright\/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodies (ANAs). Consistent with our findings in mice, we observed that human systemic lupus erythematosus (SLE) patients had expanded numbers of peripheral blood ARID3a+ B cells that were associated with increased disease activity (p = 0.0038). We hypothesized that ARID3a+ na\u00efve B cells would eventually produce autoantibodies, explaining associations between ARID3a expression and disease activity in lupus. Unlike healthy controls, ARID3a was expressed in the na\u00efve B cell population in SLE patients, and we hypothesized that these might represent expansions of autoreactive cells. Therefore, monoclonal antibodies were generated from single-sorted na\u00efve B cells derived from patients with normal (ARID3aN) and high (ARID3aH) numbers of ARID3a+ B cells. We found that ARID3a expression did not correlate with autoantibody expression. Furthermore, measures of antigen specificities of autoreactive antibodies did not reveal skewing toward particular proteins. These data suggest that the association of increased disease activity in SLE with numbers of ARID3a+ B lymphocytes may be mediated by an antibody-independent mechanism.<\/jats:p>","DOI":"10.3390\/antib4040354","type":"journal-article","created":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T10:23:41Z","timestamp":1447755821000},"page":"354-368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression"],"prefix":"10.3390","volume":"4","author":[{"given":"Julie","family":"Ward","sequence":"first","affiliation":[{"name":"Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"James","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"},{"name":"Departments of Medicine and Pathology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4164-9634","authenticated-orcid":false,"given":"Carol","family":"Webb","sequence":"additional","affiliation":[{"name":"Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City,  OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.molimm.2011.09.008","article-title":"The transcription factor bright plays a role in marginal zone b lymphocyte development and autoantibody production","volume":"49","author":"Oldham","year":"2011","journal-title":"Mol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.4049\/jimmunol.178.5.2996","article-title":"Anti-nuclear antibody production and autoimmunity in transgenic mice that overexpress the transcription factor bright","volume":"178","author":"Shankar","year":"2007","journal-title":"J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1002\/art.38857","article-title":"Disease activity in systemic lupus erythematosus correlates with expression of the transcription factor at-rich-interactive domain 3a","volume":"66","author":"Ward","year":"2014","journal-title":"Arthritis Rheum."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3389\/fimmu.2012.00302","article-title":"Advances in human b cell phenotypic profiling","volume":"3","author":"Kaminski","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1084\/jem.20042251","article-title":"Defective b cell tolerance checkpoints in systemic lupus erythematosus","volume":"201","author":"Yurasov","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.4049\/jimmunol.169.5.2477","article-title":"High frequency of matrix attachment regions and cut-like protein x\/ccaat-displacement protein and b cell regulator of igh transcription binding sites flanking ig v region genes","volume":"169","author":"Goebel","year":"2002","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7460","DOI":"10.1073\/pnas.86.19.7460","article-title":"Conservation of an immunoglobulin variable-region gene family indicates a specific, noncoding function","volume":"86","author":"Tutter","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1128\/IAI.70.8.4083-4091.2002","article-title":"Recurrent variable region gene usage and somatic mutation in the human antibody response to the capsular polysaccharide of streptococcus pneumoniae type 23f","volume":"70","author":"Zhou","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1172\/JCI27628","article-title":"Mature b cells class switched to igd are autoreactive in healthy individuals","volume":"117","author":"Koelsch","year":"2007","journal-title":"J. Clin. Invest."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/art.10561","article-title":"American College of Rheumatology Ad Hoc Committee on Immunologic Testing, G. Evidence-based guidelines for the use of immunologic tests: Antinuclear antibody testing","volume":"47","author":"Solomon","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.coi.2008.09.001","article-title":"B-cell tolerance checkpoints in health and autoimmunity","volume":"20","author":"Meffre","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1126\/science.1086907","article-title":"Predominant autoantibody production by early human b cell precursors","volume":"301","author":"Wardemann","year":"2003","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E1399","DOI":"10.1073\/pnas.1107830108","article-title":"The inflammatory cytokine il-18 induces self-reactive innate antibody responses regulated by natural killer t cells","volume":"108","author":"Enoksson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e16857","DOI":"10.1371\/journal.pone.0016857","article-title":"Comparison of antibody repertoires produced by hiv-1 infection, other chronic and acute infections, and systemic autoimmune disease","volume":"6","author":"Breden","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molimm.2004.07.049","article-title":"Adult lupus-prone mrl\/mpj2+ mice express a primary antibody repertoire that differs in cdr-h3 length distribution and hydrophobicity from that expressed in the c3h parental strain","volume":"42","author":"Zemlin","year":"2005","journal-title":"Mol. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1515\/cclm-2012-0191","article-title":"Current state of diagnostic technologies in the autoimmunology laboratory","volume":"51","author":"Tozzoli","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1590\/S1806-37132011000100015","article-title":"Myositis-related interstitial lung disease and antisynthetase syndrome","volume":"37","author":"Solomon","year":"2011","journal-title":"J. Bras. Pneumol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1002\/art.1780400928","article-title":"Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1016\/j.vaccine.2012.03.002","article-title":"Human monoclonal antibodies generated following vaccination with ava provide neutralization by blocking furin cleavage but not by preventing oligomerization","volume":"30","author":"Smith","year":"2012","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nprot.2009.3","article-title":"Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen","volume":"4","author":"Smith","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nature06890","article-title":"Rapid cloning of high-affinity human monoclonal antibodies against influenza virus","volume":"453","author":"Wrammert","year":"2008","journal-title":"Nature"},{"key":"ref_22","unstructured":"IMGT\u00ae, the international immunogenetics information system\u00ae. Available online: http:\/\/www.imgt.org\/."}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/4\/4\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:52:16Z","timestamp":1760215936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/4\/4\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,17]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["antib4040354"],"URL":"https:\/\/doi.org\/10.3390\/antib4040354","relation":{},"ISSN":["2073-4468"],"issn-type":[{"type":"electronic","value":"2073-4468"}],"subject":[],"published":{"date-parts":[[2015,11,17]]}}}