{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:13:49Z","timestamp":1789964029752,"version":"4.0.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T00:00:00Z","timestamp":1438819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>B cells are known to instigate and promulgate immune responses by producing antibodies and presenting antigens to T cells. However, a rare but potent B-cell subset in both humans and mice is capable of inhibiting immune responses through the production of the anti-inflammatory cytokine IL-10. Regulatory B cells do not express any unique combination of surface markers but instead represent a small population of B cells that have acquired the unique ability to produce IL-10. This numerically rare B-cell subset is therefore functionally referred to as \u2018B10 cells\u2019 to reflect both their molecular program and the fact that their anti-inflammatory effects in models of autoimmunity, infection and cancer are solely attributable to IL-10 production. As with most B cells, B10 cell development and function appear to be predominantly, if not exclusively, driven by antigen-receptor signals. Once generated, B10 cells respond to both innate and adaptive immune signals, with a requirement for antigen-specific local interactions with T cells to induce IL-10 production and to provide optimal immune suppression in mouse models of autoimmune disease. B10 cells therefore provide an antigen-specific mechanism for delivering IL-10 locally to sites of immune activation and inflammation. The ability of B10 cells to regulate innate and adaptive immune responses makes them an ideal therapeutic target for the treatment of many immune-related disorders.<\/jats:p>","DOI":"10.1093\/intimm\/dxv046","type":"journal-article","created":{"date-parts":[[2015,8,8]],"date-time":"2015-08-08T00:09:27Z","timestamp":1438992567000},"page":"471-477","source":"Crossref","is-referenced-by-count":127,"title":["Regulatory B10 cell development and function"],"prefix":"10.1093","volume":"27","author":[{"given":"Jacquelyn M.","family":"Lykken","sequence":"first","affiliation":[{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Candando","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Tedder","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,6]]},"reference":[{"key":"2022072000282766100_CIT0001","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/intimm\/12.5.597","article-title":"Regulatory role of mature B cells in a murine model of inflammatory bowel disease","volume":"12","author":"Mizoguchi","year":"2000","journal-title":"Int. Immunol"},{"key":"2022072000282766100_CIT0002","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.4049\/jimmunol.167.2.1081","article-title":"Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice","volume":"167","author":"Tian","year":"2001","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0003","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/ni833","article-title":"B cells regulate autoimmunity by provision of IL-10","volume":"3","author":"Fillatreau","year":"2002","journal-title":"Nat. Immunol"},{"key":"2022072000282766100_CIT0004","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1084\/jem.20021293","article-title":"Prevention of arthritis by interleukin 10-producing B cells","volume":"197","author":"Mauri","year":"2003","journal-title":"J. Exp. Med"},{"key":"2022072000282766100_CIT0005","doi-asserted-by":"crossref","first-page":"14080","DOI":"10.1073\/pnas.0700326104","article-title":"Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells","volume":"104","author":"Gray","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022072000282766100_CIT0006","doi-asserted-by":"crossref","first-page":"7868","DOI":"10.4049\/jimmunol.178.12.7868","article-title":"Novel suppressive function of transitional 2 B cells in experimental arthritis","volume":"178","author":"Evans","year":"2007","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0007","first-page":"3420","article-title":"Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression","volume":"118","author":"Matsushita","year":"2008","journal-title":"J. Clin. Invest"},{"key":"2022072000282766100_CIT0008","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.4049\/jimmunol.0803052","article-title":"Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL\/lpr mice","volume":"182","author":"Blair","year":"2009","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0009","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.4049\/jimmunol.0902391","article-title":"Protective and pathogenic roles for B cells during systemic autoimmunity in NZB\/W F1 mice","volume":"184","author":"Haas","year":"2010","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0010","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.4049\/jimmunol.1001307","article-title":"Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling EAE initiation and late-phase immunopathogenesis","volume":"185","author":"Matsushita","year":"2010","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0011","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.immuni.2008.03.017","article-title":"A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses","volume":"28","author":"Yanaba","year":"2008","journal-title":"Immunity"},{"key":"2022072000282766100_CIT0012","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.4049\/jimmunol.0902385","article-title":"Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity","volume":"184","author":"Watanabe","year":"2010","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0013","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.jaci.2010.01.018","article-title":"Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model","volume":"125","author":"Amu","year":"2010","journal-title":"J. Allergy Clin. Immunol"},{"key":"2022072000282766100_CIT0014","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/eji.1830220314","article-title":"Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10","volume":"22","author":"O\u2019Garra","year":"1992","journal-title":"Eur. J. Immunol"},{"key":"2022072000282766100_CIT0015","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1084\/jem.186.10.1749","article-title":"Suppressive role of B cells in chronic colitis of T cell receptor \u03b1 mutant mice","volume":"186","author":"Mizoguchi","year":"1997","journal-title":"J. Exp. Med"},{"key":"2022072000282766100_CIT0016","doi-asserted-by":"crossref","first-page":"705","DOI":"10.4049\/jimmunol.176.2.705","article-title":"A case for regulatory B cells","volume":"176","author":"Mizoguchi","year":"2006","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0017","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-60761-869-0_7","article-title":"Identifying regulatory B cells (B10 cells) that produce IL-10","volume":"677","author":"Matsushita","year":"2011","journal-title":"Methods Mol. Biol"},{"key":"2022072000282766100_CIT0018","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2010-07-294249","article-title":"Characterization of a rare IL-10-competent B cell subset in humans that parallels mouse regulatory B10 cells","volume":"117","author":"Iwata","year":"2011","journal-title":"Blood"},{"key":"2022072000282766100_CIT0019","doi-asserted-by":"crossref","first-page":"7459","DOI":"10.4049\/jimmunol.0900270","article-title":"The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals","volume":"182","author":"Yanaba","year":"2009","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0020","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature11501","article-title":"Regulatory B cells control T cell autoimmunity through IL-21-dependent cognate interactions","volume":"491","author":"Yoshizaki","year":"2012","journal-title":"Nature"},{"key":"2022072000282766100_CIT0021","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.4049\/jimmunol.1300649","article-title":"Peritoneal cavity regulatory B cells (B10 cells) modulate IFN-\u03d2+ CD4+ T cell numbers during colitis development in mice","volume":"191","author":"Maseda","year":"2013","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0022","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1172\/JCI46274","article-title":"Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice","volume":"121","author":"Ding","year":"2011","journal-title":"J. Clin. Invest"},{"key":"2022072000282766100_CIT0023","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1074-7613(02)00274-1","article-title":"Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation","volume":"16","author":"Mizoguchi","year":"2002","journal-title":"Immunity"},{"key":"2022072000282766100_CIT0024","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/nm.3680","article-title":"Regulatory B cells are induced by gut microbiota-driven interleukin-1beta and interleukin-6 production","volume":"20","author":"Rosser","year":"2014","journal-title":"Nat. Med"},{"key":"2022072000282766100_CIT0025","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.immuni.2014.10.016","article-title":"Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation","volume":"41","author":"Matsumoto","year":"2014","journal-title":"Immunity"},{"key":"2022072000282766100_CIT0026","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.4049\/jimmunol.1201427","article-title":"Regulatory B cell (B10 cell) expansion during Listeria infection governs innate and cellular immune responses in mice","volume":"190","author":"Horikawa","year":"2013","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0027","doi-asserted-by":"crossref","first-page":"6092","DOI":"10.4049\/jimmunol.178.10.6092","article-title":"Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis","volume":"178","author":"Duddy","year":"2007","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0028","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.immuni.2009.11.009","article-title":"CD19+CD24hiCD38hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients","volume":"32","author":"Blair","year":"2010","journal-title":"Immunity"},{"key":"2022072000282766100_CIT0029","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.4049\/jimmunol.1102500","article-title":"Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo","volume":"188","author":"Maseda","year":"2012","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0030","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"Saraiva","year":"2010","journal-title":"Nat. Rev. Immunol"},{"key":"2022072000282766100_CIT0031","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1073\/pnas.1109173109","article-title":"A tolerogenic role for Toll-like receptor 9 is revealed by B-cell interaction with DNA complexes expressed on apoptotic cells","volume":"109","author":"Miles","year":"2012","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022072000282766100_CIT0032","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nature12979","article-title":"IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases","volume":"507","author":"Shen","year":"2014","journal-title":"Nature"},{"key":"2022072000282766100_CIT0033","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jaut.2014.01.032","article-title":"IL-10-producing regulatory B cells induced by IL-33 (BregIL-33) effectively attenuate mucosal inflammatory responses in the gut","volume":"50","author":"Sattler","year":"2014","journal-title":"J. Autoimmun"},{"key":"2022072000282766100_CIT0034","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nm.3554","article-title":"Interleukin-35 induces regulatory B cells that suppress autoimmune disease","volume":"20","author":"Wang","year":"2014","journal-title":"Nat. Med"},{"key":"2022072000282766100_CIT0035","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nrrheum.2014.95","article-title":"Autoimmunity: regulatory B cells\u2013IL-35 and IL-21 regulate the regulators","volume":"10","author":"Tedder","year":"2014","journal-title":"Nat. Rev. Rheumatol"},{"key":"2022072000282766100_CIT0036","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12026-011-8209-y","article-title":"Molecular interactions within the IL-6\/IL-12 cytokine\/receptor superfamily","volume":"51","author":"Jones","year":"2011","journal-title":"Immunol. Res"},{"key":"2022072000282766100_CIT0037","doi-asserted-by":"crossref","first-page":"e107990","DOI":"10.1371\/journal.pone.0107990","article-title":"Recombinant p35 from bacteria can form Interleukin (IL-)12, but Not IL-35","volume":"9","author":"Aparicio-Siegmund","year":"2014","journal-title":"PLoS One"},{"key":"2022072000282766100_CIT0038","doi-asserted-by":"crossref","first-page":"812","DOI":"10.2353\/ajpath.2006.050923","article-title":"Inhibitory role of CD19 in the progression of experimental autoimmune encephalomyelitis by regulating cytokine response","volume":"168","author":"Matsushita","year":"2006","journal-title":"Am. J. Pathol"},{"key":"2022072000282766100_CIT0039","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.ajpath.2010.10.022","article-title":"IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model","volume":"178","author":"Yanaba","year":"2011","journal-title":"Am. J. Pathol"},{"key":"2022072000282766100_CIT0040","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.ajpath.2012.03.010","article-title":"IL-10-producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generation","volume":"180","author":"Yang","year":"2012","journal-title":"Am. J. Pathol"},{"key":"2022072000282766100_CIT0041","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1182\/blood-2012-11-465658","article-title":"Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease","volume":"121","author":"Le Huu","year":"2013","journal-title":"Blood"},{"key":"2022072000282766100_CIT0042","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrrheum.2009.184","article-title":"CD19: a promising B cell target for rheumatoid arthritis","volume":"5","author":"Tedder","year":"2009","journal-title":"Nat. Rev. Rheumatol"},{"key":"2022072000282766100_CIT0043","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s12026-010-8189-3","article-title":"B-lymphocyte effector functions in health and disease","volume":"49","author":"DiLillo","year":"2011","journal-title":"Immunol. Res"},{"key":"2022072000282766100_CIT0044","doi-asserted-by":"crossref","first-page":"678","DOI":"10.4049\/jimmunol.1102456","article-title":"B cell-derived IL-10 does not regulate spontaneous systemic autoimmunity in MRL.Fas(lpr) mice","volume":"188","author":"Teichmann","year":"2012","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0045","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":"2022072000282766100_CIT0046","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1586\/14737175.9.3.309","article-title":"B-lymphocyte depletion for the treatment of multiple sclerosis: now things really get interesting","volume":"9","author":"Matsushita","year":"2009","journal-title":"Expert Rev. Neurother"},{"key":"2022072000282766100_CIT0047","doi-asserted-by":"crossref","first-page":"e22464","DOI":"10.1371\/journal.pone.0022464","article-title":"Amplified B lymphocyte CD40 signaling drives regulatory B10 cell expansion in mice","volume":"6","author":"Poe","year":"2011","journal-title":"PLoS One"},{"key":"2022072000282766100_CIT0048","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/imr.12176","article-title":"B10 cell regulation of health and disease","volume":"259","author":"Candando","year":"2014","journal-title":"Immunol. Rev"},{"key":"2022072000282766100_CIT0049","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.4049\/jimmunol.1401329","article-title":"B10 cells: a functionally defined regulatory B cell subset","volume":"194","author":"Tedder","year":"2015","journal-title":"J. Immunol"},{"key":"2022072000282766100_CIT0050","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.immuni.2010.10.016","article-title":"Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection","volume":"33","author":"Neves","year":"2010","journal-title":"Immunity"},{"key":"2022072000282766100_CIT0051","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1172\/JCI59266","article-title":"Regulatory B cell production of IL-10 inhibits lymphoma depletion during CD20 immunotherapy in mice","volume":"121","author":"Horikawa","year":"2011","journal-title":"J. Clin. Invest"},{"key":"2022072000282766100_CIT0052","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/leu.2012.165","article-title":"Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function","volume":"27","author":"DiLillo","year":"2012","journal-title":"Leukemia"},{"key":"2022072000282766100_CIT0053","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1073\/pnas.102181599","article-title":"Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression","volume":"99","author":"Bichi","year":"2002","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/27\/10\/471\/45027538\/intimm_27_10_471.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/27\/10\/471\/45027538\/intimm_27_10_471.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:29:11Z","timestamp":1658276951000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/27\/10\/471\/705536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,6]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2015,8,6]]},"published-print":{"date-parts":[[2015,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxv046","relation":{},"ISSN":["1460-2377","0953-8178"],"issn-type":[{"value":"1460-2377","type":"electronic"},{"value":"0953-8178","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,10]]},"published":{"date-parts":[[2015,8,6]]}}}