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J Immunol. 2018 Oct 1;201(7):1865-1874. doi: 10.4049/jimmunol.1800206. Epub 2018 Aug 20.

Differential Influence on Regulatory B Cells by TH2 Cytokines Affects Protection in Allergic Airway Disease.

Author information

1
Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.
2
Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; and.
3
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109.
4
Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; sklundy@med.umich.edu.

Abstract

The role of regulatory B cells (Bregs) in modulating immune responses and maintaining tolerance are well established. However, how cytokines present during immune responses affect Breg growth and function are not as well defined. Previously, our laboratory reported IL-5- and mCD40L-expressing fibroblast (mCD40L-Fb) stimulation induced IL-10 production from murine B cells. The current study investigated the phenotype and functional relevance of IL-10- producing B cells from this culture. We found IL-5/mCD40L-Fb stimulation induced IL-10 production exclusively from CD5+ splenic B cells of naive mice. After stimulation, the resulting IL-10+ B cells displayed markers of multiple reported Breg phenotypes. Interestingly, when investigating effects of IL-4 (a critical TH2 cytokine) on IL-5/mCD40L-Fb-induced IL-10 production, we found IL-4 inhibited IL-10 production in a STAT6-dependent manner. Upon adoptive transfer, CD5+ B cells previously stimulated with IL-5/mCD40L-Fb were able to reduce development of OVA-induced allergic airway disease in mice. Using B cells from IL-10 mutant mice differentiated by IL-5/mCD40L-Fb, we found protection from allergic airway disease development was dependent on the IL-10 production from the transferred B cells. Bregs have been shown to play crucial roles in the immune tolerance network, and understanding stimuli that modulate their growth and function may be key in development of future treatments for diseases of immune dysregulation.

PMID:
30127086
PMCID:
PMC6143409
[Available on 2019-10-01]
DOI:
10.4049/jimmunol.1800206

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