{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:28:58Z","timestamp":1792448938612,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":2228,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Controlled allergic disease is associated with decreased allergen-specific IgE and increased allergen-specific IgG4. Although IL-10 has been shown to contribute to these changes, the underlying mechanisms are largely unknown. This study explored how IL-10 differentially regulates human IgE and IgG4 production. Highly purified B cells and B cell subsets from healthy individuals were cultured with combinations of anti-CD40, IL-4, and IL-10. In other experiments, PBMCs isolated from healthy donors or from autosomal dominant hyper-IgE syndrome (STAT3 loss-of-function) subjects were cultured with combinations of IL-4 and IL-10. In B cell cultures, IL-10 had no significant effect on IL-4\u2013induced IgE production but increased IL-4\u2013induced IgG4 production over 20-fold. IL-4\u2013induced transcription of C\u03b5 and C\u03b34 germline transcripts (GLTs) by isolated B cells was not affected by IL-10. In PBMC cultures, IL-4 induced production of both IgE and IgG4 and increased expression of C\u03b5 and C\u03b34 GLTs above baseline. Unlike in purified B cells, IL-10 diminished IL-4\u2013induced IgE production and expression of C\u03b5 GLTs without affecting IgG4 production or expression of C\u03b34 GLTs. PBMCs from autosomal dominant hyper-IgE syndrome individuals failed to consistently modulate IgE production in response to IL-4 and IL-10. As measured by flow cytometry, the frequency of IL-10R+ cells was similar between IgE+ and IgG4+ B cells. These data suggest that IL-10 acts indirectly through accessory cells to modulate the production of IgE. For IgG4, IL-10 appears to act directly on B cells to drive IgG4 production, with its effects being downstream of germline transcription.<\/jats:p>","DOI":"10.4049\/immunohorizons.1800076","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T23:15:16Z","timestamp":1545174916000},"page":"398-406","source":"Crossref","is-referenced-by-count":42,"title":["IL-10 Indirectly Downregulates IL-4\u2013Induced IgE Production by Human B Cells"],"prefix":"10.1093","volume":"2","author":[{"given":"Adora A","family":"Lin","sequence":"first","affiliation":[{"name":"Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra F","family":"Freeman","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6887-4941","authenticated-orcid":false,"given":"Thomas B","family":"Nutman","sequence":"additional","affiliation":[{"name":"Helminth Immunology Section, Laboratory of Parasitic Diseases, 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":[[2018,12,19]]},"reference":[{"key":"2025010608380639000_r1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.4049\/jimmunol.130.2.722","article-title":"Serologic aspects of IgG4 antibodies. 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