Elevated IL-10 is Linked With the Expansion of T-bet^highCD21^low B Cells in Patients With Common Variable Immunodeficiency.

Authors

Victoria Cousin, Anna Graumann, Valerie Geiger, David Sökler, Patrick Bez, Sylvia Gutenberger, Cornelia Glaser, Geoffroy Andrieux, Melanie Boerries, Björn Christian Frye, Gernot Zissel, Celia Lourdes Calvillo, Javier Rodriguez-Ubreva, Esteban Ballestar, Fabian Hauck, Reinhard E Voll, Nina Chevalier, Baerbel Keller, Klaus Warnatz

Published in

Journal of clinical immunology. Volume 46. Issue 1. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Common variable immunodeficiency (CVID) is frequently complicated by autoimmune and inflammatory manifestations associated with profound immune dysregulation (CVIDc), including expansion of T-bet^highCD21^low B cells (CD21^low B cells). Elevated serum IL-10 levels have repeatedly been reported in CVIDc, yet their relationship to CD21^low B-cell differentiation remains unclear. In this study, we determined a significant correlation between increased serum IL-10 levels and frequency of circulating CD21^low 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^low B cells in peripheral blood and inflamed tissues. CD21^low B cells expressed elevated levels of IL-10 receptor subunits and displayed intact IL-10-induced STAT3 signaling, indicating preserved responsiveness to IL-10. Functionally, IL-10 alone neither induced CD21^low B-cell differentiation nor inhibited IFN-γ-driven polarization. However, in vitro differentiation assays showed that IL-10 can substitute for IL-21 during CD40L/T cell-dependent differentiation of CD21^low-like B cells and promote their survival in vitro. These findings suggest that IL-10 may support the expansion and persistence of CD21^low B cells at inflammatory sites. Collectively, our data identify IL-10 as a component of the inflammatory environment associated with CD21^low 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.

PMID:
42603226
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.