{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:06:34Z","timestamp":1789376794118,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"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":[[2013,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bcl-3 is an atypical member of the family of I\u03baB proteins. Unlike the classic members, Bcl-3 functions as a nuclear transcriptional cofactor that may, depending on context, promote or suppress genes via association with p50\/NF-\u03baB1 or p52\/NF-\u03baB2 homodimers. Bcl-3 is also an oncogene, because it is a partner in recurrent translocations in B cell tumors, resulting in deregulated expression. Bcl-3 functions, however, remain poorly understood. We have investigated the role of Bcl-3 in B cells and discovered a previously unknown involvement in the splenic development of these cells. Loss of Bcl-3 in B cells resulted in significantly more marginal zone (MZ) and fewer follicular (FO) B cells. Conversely, transgenic expression of Bcl-3 in B cells generated fewer MZ and more FO B cells. Both Bcl-3\u2212\/\u2212 FO and MZ B cells were more responsive to LPS stimulation compared with their wild-type counterparts, including increased proliferation. By contrast, Bcl-3\u2212\/\u2212 FO B cells were more prone to apoptosis upon BCR stimulation, also limiting their expansion. The data reveal Bcl-3 as a regulator of B cell fate determination, restricting the MZ path and favoring the FO pathway, at least in part, via increased signal-specific survival of the latter, a finding of relevance to its tumorigenic activity.<\/jats:p>","DOI":"10.4049\/jimmunol.1300611","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T03:43:24Z","timestamp":1384573404000},"page":"5984-5992","source":"Crossref","is-referenced-by-count":28,"title":["The Tumor Promoter and NF-\u03baB Modulator Bcl-3 Regulates Splenic B Cell Development"],"prefix":"10.1093","volume":"191","author":[{"given":"Xiaoren","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"},{"name":"Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine , Shanghai 200031,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Paun","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Claudio","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Siebenlist","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,15]]},"reference":[{"key":"2025032406060400100_r1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in NF-kappaB signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"2025032406060400100_r2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nri1629","article-title":"Control of lymphocyte development by nuclear factor-kappaB","volume":"5","author":"Siebenlist","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406060400100_r3","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/0092-8674(90)90347-H","article-title":"The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control","volume":"60","author":"Ohno","year":"1990","journal-title":"Cell"},{"key":"2025032406060400100_r4","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1182\/blood-2002-08-2464","article-title":"High-level expression of BCL3 differentiates t(2;5)(p23;q35)-positive anaplastic large cell lymphoma from Hodgkin disease","volume":"101","author":"Nishikori","year":"2003","journal-title":"Blood"},{"key":"2025032406060400100_r5","first-page":"2057","article-title":"Molecular characterization of the t(14;19)(q32;q13) translocation in chronic lymphocytic leukemia","volume":"7","author":"Ohno","year":"1993","journal-title":"Leukemia"},{"key":"2025032406060400100_r6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1532\/IJH97.05045","article-title":"Reappraisal of BCL3 as a molecular marker of anaplastic large cell lymphoma","volume":"82","author":"Ohno","year":"2005","journal-title":"Int. J. Hematol."},{"key":"2025032406060400100_r7","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1182\/blood-2003-04-1366","article-title":"BCL-3 overexpression in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma","volume":"102","author":"Rassidakis","year":"2003","journal-title":"Blood"},{"key":"2025032406060400100_r8","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1600-0609.2009.01225.x","article-title":"High expression of BCL3 in human myeloma cells is associated with increased proliferation and inferior prognosis","volume":"82","author":"Brenne","year":"2009","journal-title":"Eur. J. Haematol."},{"key":"2025032406060400100_r9","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/modpathol.3800140","article-title":"Immunohistochemical detection of BCL-3 in lymphoid neoplasms: a survey of 353 cases","volume":"17","author":"Canoz","year":"2004","journal-title":"Mod. Pathol."},{"key":"2025032406060400100_r10","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/j.1600-0609.2011.01684.x","article-title":"BCL3 rearrangement, amplification and expression in diffuse large B-cell lymphoma","volume":"87","author":"Ibrahim","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"2025032406060400100_r11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1476-4598-10-152","article-title":"Role of Bcl-3 in solid tumors","volume":"10","author":"Maldonado","year":"2011","journal-title":"Mol. Cancer"},{"key":"2025032406060400100_r12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1101\/gad.1352206","article-title":"Expression of the Bcl-3 proto-oncogene suppresses p53 activation","volume":"20","author":"Kashatus","year":"2006","journal-title":"Genes Dev."},{"key":"2025032406060400100_r13","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.1128\/MCB.23.13.4713-4727.2003","article-title":"p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1","volume":"23","author":"Rocha","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"2025032406060400100_r14","doi-asserted-by":"crossref","first-page":"8428","DOI":"10.1128\/MCB.21.24.8428-8436.2001","article-title":"The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G(1) transition","volume":"21","author":"Westerheide","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2025032406060400100_r15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/intimm\/dxp002","article-title":"Transgenic Bcl-3 slows T cell proliferation","volume":"21","author":"Bassetti","year":"2009","journal-title":"Int. Immunol."},{"key":"2025032406060400100_r16","doi-asserted-by":"crossref","first-page":"7297","DOI":"10.1038\/sj.onc.1209711","article-title":"BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription","volume":"25","author":"Brocke-Heidrich","year":"2006","journal-title":"Oncogene"},{"key":"2025032406060400100_r17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1349-7006.2005.00078.x","article-title":"Stimulation of CD30 in anaplastic large cell lymphoma leads to production of nuclear factor-kappaB p52, which is associated with hyperphosphorylated Bcl-3","volume":"96","author":"Nishikori","year":"2005","journal-title":"Cancer Sci."},{"key":"2025032406060400100_r18","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1128\/IAI.01749-05","article-title":"CD8 T cells require Bcl-3 for maximal gamma interferon production upon secondary exposure to antigen","volume":"74","author":"Chilton","year":"2006","journal-title":"Infect. Immun."},{"key":"2025032406060400100_r19","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S1074-7613(00)80291-5","article-title":"Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions","volume":"6","author":"Franzoso","year":"1997","journal-title":"Immunity"},{"key":"2025032406060400100_r20","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.4049\/jimmunol.1001331","article-title":"The I\u03baB family member Bcl-3 coordinates the pulmonary defense against Klebsiella pneumoniae infection","volume":"186","author":"P\u00e8ne","year":"2011","journal-title":"J. Immunol."},{"key":"2025032406060400100_r21","doi-asserted-by":"crossref","first-page":"3560","DOI":"10.4049\/jimmunol.175.6.3560","article-title":"The IkappaB protein Bcl-3 negatively regulates transcription of the IL-10 gene in macrophages","volume":"175","author":"Riemann","year":"2005","journal-title":"J. Immunol."},{"key":"2025032406060400100_r22","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.2337\/db10-0480","article-title":"Roles of Bcl-3 in the pathogenesis of murine type 1 diabetes","volume":"59","author":"Ruan","year":"2010","journal-title":"Diabetes"},{"key":"2025032406060400100_r23","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1101\/gad.11.2.187","article-title":"Immunological defects in mice with a targeted disruption in Bcl-3","volume":"11","author":"Schwarz","year":"1997","journal-title":"Genes Dev."},{"key":"2025032406060400100_r24","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.immuni.2007.07.017","article-title":"A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance","volume":"27","author":"Zhang","year":"2007","journal-title":"Immunity"},{"key":"2025032406060400100_r25","doi-asserted-by":"crossref","first-page":"4123","DOI":"10.1182\/blood-2003-04-1228","article-title":"IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-alpha production in macrophages","volume":"102","author":"Kuwata","year":"2003","journal-title":"Blood"},{"key":"2025032406060400100_r26","doi-asserted-by":"crossref","first-page":"49995","DOI":"10.1074\/jbc.M404246200","article-title":"BCL-3 and NF-kappaB p50 attenuate lipopolysaccharide-induced inflammatory responses in macrophages","volume":"279","author":"Wessells","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025032406060400100_r27","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1126\/science.1142953","article-title":"Negative regulation of toll-like receptor signaling by NF-kappaB p50 ubiquitination blockade","volume":"317","author":"Carmody","year":"2007","journal-title":"Science"},{"key":"2025032406060400100_r28","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1002\/art.10675","article-title":"Bcl-3 is an interleukin-1-responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene","volume":"46","author":"Elliott","year":"2002","journal-title":"Arthritis Rheum."},{"key":"2025032406060400100_r29","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1182\/blood.V93.12.4318","article-title":"Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction","volume":"93","author":"Richard","year":"1999","journal-title":"Blood"},{"key":"2025032406060400100_r30","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1084\/jem.20070318","article-title":"Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD","volume":"204","author":"H\u00f6velmeyer","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025032406060400100_r31","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.1128\/MCB.01600-09","article-title":"The repressing function of the oncoprotein BCL-3 requires CtBP, while its polyubiquitination and degradation involve the E3 ligase TBLR1","volume":"30","author":"Keutgens","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"2025032406060400100_r32","doi-asserted-by":"crossref","first-page":"25831","DOI":"10.1074\/jbc.M110.112128","article-title":"BCL-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1","volume":"285","author":"Keutgens","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2025032406060400100_r33","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2006.03.041","article-title":"Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling","volume":"125","author":"Massoumi","year":"2006","journal-title":"Cell"},{"key":"2025032406060400100_r34","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.molcel.2004.09.004","article-title":"GSK3-mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity","volume":"16","author":"Viatour","year":"2004","journal-title":"Mol. Cell"},{"key":"2025032406060400100_r35","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.4049\/jimmunol.163.12.6581","article-title":"Distinct activities of p52\/NF-kappa B required for proper secondary lymphoid organ microarchitecture: functions enhanced by Bcl-3","volume":"163","author":"Poljak","year":"1999","journal-title":"J. Immunol."},{"key":"2025032406060400100_r36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.coi.2008.03.014","article-title":"Peripheral B cell subsets","volume":"20","author":"Allman","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"2025032406060400100_r37","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1182\/blood-2008-02-140814","article-title":"Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis","volume":"112","author":"Meyer-Bahlburg","year":"2008","journal-title":"Blood"},{"key":"2025032406060400100_r38","doi-asserted-by":"crossref","first-page":"e1000748","DOI":"10.1371\/journal.ppat.1000748","article-title":"In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells","volume":"6","author":"Wong","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032406060400100_r39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.immuni.2011.11.017","article-title":"B-1 B cell development in the fetus and adult","volume":"36","author":"Montecino-Rodriguez","year":"2012","journal-title":"Immunity"},{"key":"2025032406060400100_r40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.4049\/jimmunol.172.2.803","article-title":"Marginal zone, but not follicular B cells, are potent activators of naive CD4 T cells","volume":"172","author":"Attanavanich","year":"2004","journal-title":"J. Immunol."},{"key":"2025032406060400100_r41","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.4049\/jimmunol.153.5.1990","article-title":"Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen","volume":"153","author":"Lenschow","year":"1994","journal-title":"J. Immunol."},{"key":"2025032406060400100_r42","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nri2656","article-title":"The follicular versus marginal zone B lymphocyte cell fate decision","volume":"9","author":"Pillai","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406060400100_r43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4049\/jimmunol.179.1.195","article-title":"Synergism between NF-kappa B1\/p50 and Notch2 during the development of marginal zone B lymphocytes","volume":"179","author":"Moran","year":"2007","journal-title":"J. Immunol."},{"key":"2025032406060400100_r44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-immunol-020711-075011","article-title":"Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs","volume":"30","author":"Cyster","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"2025032406060400100_r45","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.immuni.2006.07.010","article-title":"Alternative and classical NF-kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus-like disease","volume":"25","author":"Enzler","year":"2006","journal-title":"Immunity"},{"key":"2025032406060400100_r46","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.1071632","article-title":"Integrin-mediated long-term B cell retention in the splenic marginal zone","volume":"297","author":"Lu","year":"2002","journal-title":"Science"},{"key":"2025032406060400100_r47","doi-asserted-by":"crossref","first-page":"13789","DOI":"10.1073\/pnas.0605944103","article-title":"Testing gene function early in the B cell lineage in mb1-cre mice","volume":"103","author":"Hobeika","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032406060400100_r48","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1146\/annurev.immunol.23.021704.115728","article-title":"Marginal zone B cells","volume":"23","author":"Pillai","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2025032406060400100_r49","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nri799","article-title":"Marginal-zone B cells","volume":"2","author":"Martin","year":"2002","journal-title":"Nat. Rev. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/12\/5984\/61536639\/1300611.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/12\/5984\/61536639\/1300611.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T17:52:30Z","timestamp":1742925150000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/12\/5984\/7966570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1300611","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,12]]},"published":{"date-parts":[[2013,12]]}}}