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Type III IFN (IFN-\u03bb) is now appreciated to have a nonredundant role in viral infection, but few studies have addressed the effects of IFN-\u03bb on immune cells given the more restricted expression of its receptor primarily to the epithelium. In this study, we demonstrate that B cells display a prominent IFN gene expression profile in patients with lupus. Serum levels of IFN-\u03bb are elevated in SLE and positively correlate with B cell subsets associated with autoimmune plasma cell development, including CD11c+T-bet+CD21\u2212 B cells. Although B cell subsets express all IFN receptors, IFNLR1 strongly correlates with the CD11c+CD21\u2212 B cell expansion, suggesting that IFN-\u03bb may be an unappreciated driver of the SLE IFN signature and B cell abnormalities. We show that IFN-\u03bb potentiates gene transcription in human B cells typically attributed to type I IFN as well as expansion of T-bet\u2013expressing B cells after BCR and TLR7\/8 stimulation. Further, IFN-\u03bb promotes TLR7\/8-mediated plasmablast differentiation and increased IgM production. CD11c+ B cells demonstrate IFN-\u03bb hyperresponsive signaling compared with other B cell subsets, suggesting that IFN-\u03bb accelerates plasma cell differentiation through this putative extrafollicular pathway. In summary, our data support type III IFN-\u03bb as a cytokine promoting the Ab-secreting cell pool in human viral and autoimmune disease.<\/jats:p>","DOI":"10.4049\/jimmunol.2100339","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T22:30:22Z","timestamp":1637620222000},"page":"2660-2672","source":"Crossref","is-referenced-by-count":40,"title":["B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-\u03bb in Systemic Lupus Erythematosus"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-4403","authenticated-orcid":false,"given":"Jennifer L","family":"Barnas","sequence":"first","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2868-3339","authenticated-orcid":false,"given":"Nida","family":"Meednu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-4478","authenticated-orcid":false,"given":"Diana F","family":"Alzamareh","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3792-4317","authenticated-orcid":false,"given":"Cameron","family":"Baker","sequence":"additional","affiliation":[{"name":"University of Rochester Genomics Research Center, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-1213","authenticated-orcid":false,"given":"Andrew","family":"McDavid","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R John","family":"Looney","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H","family":"Anolik","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"2025022610323062200_r1","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1056\/NEJMoa2001180","article-title":"Two-year, randomized, controlled trial of belimumab in lupus nephritis","volume":"383","author":"Furie","year":"2020","journal-title":"N. 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