{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:35:52Z","timestamp":1791329752556,"version":"4.3.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"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":[[2017,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10\u2013producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10\u2013 producing Bregs in RA. Our aim was to identify the optimal conditions that induce IL-10+ Bregs and, furthermore, to shed light on the signaling pathways that are responsible for their expansion. The results show that dual stimulation by CpG and CD40L for 48 h is optimal for IL-10 induction, and this can be synergistically boosted by IL-21. We identified the CD19+CD27+ memory B cell population as the major source of IL-10+ Bregs. We detected significantly fewer CD19+CD27+IL-10+ cells in RA patients compared with healthy controls, and these were functionally defective in suppressing IFN-\u03b3 production by CD4+ T cells in coculture. IL-21 drastically increased the number of IL-10+ Bregs within the CD19+CD27+ and CD19+CD27\u2212 populations; furthermore, it induced the appearance of IL-10+Blimp-1+ plasmablasts. Monitoring the phosphorylation of key signaling molecules revealed that activation of ERK, p38, and CREB is indispensable for the induction of IL-10 production, whereas phosphorylation of STAT3 further enhances IL-10 expression in human Bregs. We conclude that CREB and STAT3 are the key transcription factors responsible for the expansion and differentiation of human IL-10\u2013producing Bregs.<\/jats:p>","DOI":"10.4049\/jimmunol.1600218","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T21:40:28Z","timestamp":1484343628000},"page":"1512-1520","source":"Crossref","is-referenced-by-count":119,"title":["Induction and Differentiation of IL-10\u2013Producing Regulatory B Cells from Healthy Blood Donors and Rheumatoid Arthritis Patients"],"prefix":"10.1093","volume":"198","author":[{"given":"Zsuzsanna","family":"Bank\u00f3","sequence":"first","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University , Budapest, 1117","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Pozsgay","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University , Budapest, 1117","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-1624","authenticated-orcid":false,"given":"D\u00e1niel","family":"Szili","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University , Budapest, 1117","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7620-2889","authenticated-orcid":false,"given":"M\u00e1ria","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University , Budapest, 1117","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7549-8291","authenticated-orcid":false,"given":"Tam\u00e1s","family":"G\u00e1ti","sequence":"additional","affiliation":[{"name":"Buda Hospital of Hospitaller Brothers of St. John , Budapest, 1023","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Nagy","sequence":"additional","affiliation":[{"name":"Buda Hospital of Hospitaller Brothers of St. John , Budapest, 1023","place":["Hungary"]},{"name":"Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University , Budapest, 1023","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Rojkovich","sequence":"additional","affiliation":[{"name":"Buda Hospital of Hospitaller Brothers of St. John , Budapest, 1023","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-7768","authenticated-orcid":false,"given":"Gabriella","family":"S\u00e1rmay","sequence":"additional","affiliation":[{"name":"Department of Immunology, E\u00f6tv\u00f6s Lor\u00e1nd University , Budapest, 1117","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,15]]},"reference":[{"key":"2025030615024064500_r1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-immunol-020711-074934","article-title":"Immune regulatory function of B cells","volume":"30","author":"Mauri","year":"2012","journal-title":"Annu. 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