Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits Fc is an element of RI-induced mast cell activation when the two receptors are colig ated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhi bited a significantly increased sensitivity to IgE-dependent passive cutane ous anaphylaxis as assessed by greater tissue swelling and mast cell degran ulation in situ. Importantly, by the same criteria, the absence of gp49B1 a lso resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 r esulted in a significantly: greater and faster death rate in active systemi c anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation i n vivo. In addition, this study provides a new concept and target for regul ation of allergic disease susceptibility and severity.