B cell lymphoma 10 is essential for FcεR-mediated degranulation and IL-6 production in mast cells

The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the functions of the AgRs in T and B cells. In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of Fc epsilon R. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired Fc epsilon R-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bc10-deficient mast cells have normal Fc epsilon R-mediated Ca2+ flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished Fc epsilon R-mediated activation of NF-kappa B and decreased activation of AP-1. Thus, Bcl10 is essential for Fc epsilon R-induced activation of AP-1, NF-kappa B, degranulation, and cytokine production in mast cells.