Research ArticleImmunology

Interleukin-10–producing CD5+ B cells inhibit mast cells during immunoglobulin E–mediated allergic responses

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Sci. Signal.  17 Mar 2015:
Vol. 8, Issue 368, pp. ra28
DOI: 10.1126/scisignal.2005861

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Limiting allergic responses with B cells

B cells promote immune responses by producing antibodies; however, subsets of B cells secrete the anti-inflammatory cytokine interleukin-10 (IL-10) and have immunosuppressive properties. Kim et al. found that these B cells inhibited the activation of mast cells, immune cells that are critical regulators of allergic reactions. Indeed, mice lacking these special B cells had more severe symptoms of anaphylaxis. Mast cell inhibition required physical contact with the B cells, which stimulated the B cells to produce more IL-10. B cell–mediated inhibition of mast cells depended on IL-10, which inhibited tyrosine kinase signaling in mast cells. Thus, IL-10–producing B cells might provide a therapeutic target to treat allergic diseases.

Abstract

Subsets of B cells inhibit various immune responses through their production of the cytokine interleukin-10 (IL-10). We found that IL-10–producing CD5+ B cells suppressed the immunoglobulin E (IgE)– and antigen-mediated activation of mast cells in vitro as well as allergic responses in mice in an IL-10–dependent manner. Furthermore, the suppressive effect of these B cells on mast cells in vitro and in vivo depended on direct cell-to-cell contact through the costimulatory receptor CD40 on CD5+ B cells and the CD40 ligand on mast cells. This contact enhanced the production of IL-10 by the CD5+ B cells. Through activation of the Janus-activated kinase–signal transducer and activator of transcription 3 pathway, IL-10 decreased the abundance of the kinases Fyn and Fgr and inhibited the activation of the downstream kinase Syk in mast cells. Together, these findings suggest that an important function of IL-10–producing CD5+ B cells is inhibiting mast cells and IgE-mediated allergic responses.

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