Inhibition of anaphylactic inflammation by the gp49B1 receptor on mast cells

gp49B1 is a member of the immunoglobulin (Ig) superfamily expressed on the surface of mast cells, macrophages, and activated natural killer cells. gp49B1 inhibits FcepsilonRI-induced activation of mast cells in vitro by virtue of two immunoreceptor, tyrosine-based inhibitory motifs that recruit the SHP-1 tyrosine phosphatase to the plasma membrane. We created gp49B1 null mice by targeted gene disruption, and found that IgE-dependent mast cell activation is augmented in these animals. Moreover, the ensuing anaphylactic reactions and inflammation are enhanced in the absence of gp49B1. Thus, gp49B1 innately counter-regulates mast cell activation mediated by Ig generated through the adaptive immune response in vivo.