The FcRβ- and γ-ITAMs Play Crucial but Distinct Roles in the Full Activation of Mast Cells Induced by IgEκ and Protein L

Previous studies suggested that Protein L (PpL), the bacterial Ig-binding protein, activates mast cells. PpL presumably performs the activation by interacting with membrane-bound IgE kappa, but the underlying mechanisms behind the process remain unclear. In the current study, we found that cell-surface Fc epsilon RI expression is a critical factor participant in PpL-mediated full activation of murine mast cells, which includes cytokine production, the degranulation response, and leukotriene C-4 (LTC4) release, and that engagement of the Fc epsilon RI with IgE kappa and PpL is enough to induce tyrosine phosphorylation of ITAM in the FcR beta- and gamma-signaling subunits. Introduction of mutations in two canonical tyrosine residues (Y47F/Y58F) of the FcR gamma-ITAM completely abolished the above-mentioned mast cell functions, with the exception of LTC4 release. Importantly, the FcR beta-ITAM acts as a signal transducer that is responsible for LTC4 release independently of the FcR gamma-ITAM. Taken together, our results suggest crucial and distinct functions for the FcR beta- and gamma-ITAMs in the Fc epsilon RI-dependent full activation of mast cells induced by IgE kappa and PpL. The Journal of Immunology, 2012, 188: 4052-4064.