{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:34:40Z","timestamp":1786977280628,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["HHSN2682007000036C"],"award-info":[{"award-number":["HHSN2682007000036C"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. We undertook this study to identify molecular switches controlling pathologic B cell responses in rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Candidate molecules were identified by gene expression profiling of RA synovitis and validated by quantitative polymerase chain reaction and immunohistochemistry. B cell\u2013specific expression was confirmed by immunofluorescence, immunoblotting, and flow cytometry. The role of Bob1 in pathologic B cell responses was assessed in collagen\u2010induced arthritis (CIA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptional profiling of RA synovitis revealed a prominent B cell signature, with the transcriptional coactivator Bob1 and its putative target BCMA being among the most up\u2010regulated genes. Further analysis confirmed the microarray data and demonstrated elevated levels of Bob1 in B cells in RA synovium. A functional study showed that Bob1\u2010deficient mice failed to produce pathogenic anti\u2013type II collagen (anti\u2010CII) antibodies and were resistant to CIA. Adoptive transfer of cells from Bob1\u2010deficient and Bob1\u2010sufficient mice to recombination\u2010activating gene 1\u2013null mice demonstrated that Bob1 deficiency exclusively in B cells abrogated germinal center (GC) B cell formation, anti\u2010CII antibody production, and CIA development. Consistent with data from animal studies, immunophenotyping of human B cell subsets revealed increased expression of Bob1, predominantly in centrocytes and centroblasts. Correspondingly, Bob1 expression in RA synovitis was strongly correlated with\n                      <jats:italic>CD21L<\/jats:italic>\n                      , a molecular marker of GCs. In addition, similar Bob1 overexpression and correlation with\n                      <jats:italic>CD21L<\/jats:italic>\n                      expression was evidenced in parotid salivary gland tissue from patients with primary Sj\u00f6gren's syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These expression and functional data identify the transcriptional coactivator Bob1 as a candidate molecular switch of pathogenic B cell responses in autoimmune diseases in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39993","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T16:56:41Z","timestamp":1480611401000},"page":"750-762","source":"Crossref","is-referenced-by-count":15,"title":["The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation"],"prefix":"10.1002","volume":"69","author":[{"given":"Maria J.","family":"Levels","sequence":"first","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa N.","family":"Van Tok","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tineke","family":"Cantaert","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan D.","family":"Ca\u00f1ete","sequence":"additional","affiliation":[{"name":"Hospital Clinic of Barcelona and Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G. M.","family":"Kroese","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Germar","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hergen","family":"Spits","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam and AIMM Therapeutics Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique L. 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