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Elevated serum IL-10 levels have repeatedly been reported in CVIDc, yet their relationship to CD21\n                    <jats:sup>low<\/jats:sup>\n                    B-cell differentiation remains unclear. In this study, we determined a significant correlation between increased serum IL-10 levels and frequency of circulating CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells, particularly marked in CVIDc patients. Transcriptomic and protein analyses identified multiple cellular sources of IL-10 in CVID, including monocytes, T cells, and a subset of CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells in peripheral blood and inflamed tissues. CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells expressed elevated levels of IL-10 receptor subunits and displayed intact IL-10\u2013induced STAT3 signaling, indicating preserved responsiveness to IL-10. Functionally, IL-10 alone neither induced CD21\n                    <jats:sup>low<\/jats:sup>\n                    B-cell differentiation nor inhibited IFN-\u03b3\u2013driven polarization. However, in vitro differentiation assays showed that IL-10 can substitute for IL-21 during CD40L\/T cell\u2013dependent differentiation of CD21\n                    <jats:sup>low<\/jats:sup>\n                    -like B cells and promote their survival in vitro. These findings suggest that IL-10 may support the expansion and persistence of CD21\n                    <jats:sup>low<\/jats:sup>\n                    B cells at inflammatory sites. Collectively, our data identify IL-10 as a component of the inflammatory environment associated with CD21\n                    <jats:sup>low<\/jats:sup>\n                    B-cell expansion and suggest that IL-10 can functionally replace IL-21 during their differentiation and promote their survival in CVID-associated immune dysregulation.\n                  <\/jats:p>","DOI":"10.1007\/s10875-026-02058-2","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T06:13:43Z","timestamp":1786774423000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated IL-10 is Linked With the Expansion of T-bethighCD21low B Cells in Patients With Common Variable Immunodeficiency"],"prefix":"10.1007","volume":"46","author":[{"given":"Victoria","family":"Cousin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Graumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Geiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"S\u00f6kler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Bez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Gutenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Glaser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffroy","family":"Andrieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn Christian","family":"Frye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Zissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia Lourdes","family":"Calvillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Rodriguez-Ubreva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Ballestar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Hauck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard E.","family":"Voll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Chevalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"issue":"1","key":"2058_CR1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaip.2015.07.025","volume":"4","author":"FA Bonilla","year":"2016","unstructured":"Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. 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