Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells

Akimichi Inaba, Zewen Kelvin Tuong, Tian X. Zhao, Andrew P. Stewart, Rebeccah Mathews, Lucy Truman, Rouchelle Sriranjan, Jane Kennet, Kourosh Saeb-Parsy, Linda Wicker, Frank Waldron-Lynch, Joseph Cheriyan, John A. Todd, Ziad Mallat and Menna R. Clatworthy ()
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Akimichi Inaba: University of Cambridge Department of Medicine
Zewen Kelvin Tuong: University of Cambridge Department of Medicine
Tian X. Zhao: Division of Cardiovascular Medicine, University of Cambridge
Andrew P. Stewart: University of Cambridge Department of Medicine
Rebeccah Mathews: University of Cambridge Department of Medicine
Lucy Truman: West Suffolk Hospital
Rouchelle Sriranjan: University of Cambridge
Jane Kennet: University of Cambridge
Kourosh Saeb-Parsy: University of Cambridge
Linda Wicker: University of Oxford
Frank Waldron-Lynch: Novartis Institutes for BioMedical Research, Autoimmunity Transplantation Inflammation
Joseph Cheriyan: University of Cambridge
John A. Todd: University of Oxford
Ziad Mallat: Division of Cardiovascular Medicine, University of Cambridge
Menna R. Clatworthy: University of Cambridge Department of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Dysfunction of interleukin-10 producing regulatory B cells has been associated with the pathogenesis of autoimmune diseases, but whether regulatory B cells can be therapeutically induced in humans is currently unknown. Here we demonstrate that a subset of activated B cells expresses CD25, and the addition of low-dose recombinant IL-2 to in vitro stimulated peripheral blood and splenic human B cells augments IL-10 secretion. Administration of low dose IL-2, aldesleukin, to patients increases IL-10-producing B cells. Single-cell RNA sequencing of circulating immune cells isolated from low dose IL2-treated patients reveals an increase in plasmablast and plasma cell populations that are enriched for a regulatory B cell gene signature. The transcriptional repressor BACH2 is significantly down-regulated in plasma cells from IL-2-treated patients, BACH2 binds to the IL-10 gene promoter, and Bach2 depletion or genetic deficiency increases B cell IL-10, implicating BACH2 suppression as an important mechanism by which IL-2 may promote an immunoregulatory phenotype in B cells.

Date: 2023
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DOI: 10.1038/s41467-023-37424-w

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