RIII-dependent Mast Cell Degranulation and Anaphylaxis

In mouse mast cells, both Fc e RI and Fc g RIII are abg 2 tetrameric complexes in which different a chains confer IgE or IgG ligand recognition while the signaling FcR b and g chains are identical. We used primarily noninvasive techniques (changes in body temperature, dye extravasation) to assess systemic anaphylactic responses in nonanesthetized wild-type, Fc e RI a chain 2 / 2 and FcR g chain 2 / 2 mice. We confirm that systemic anaphylaxis in mice can be mediated largely through IgG 1 and Fc g RIII and we provide direct evidence that these responses reflect activation of Fc g RIII rather than Fc g RI. Furthermore, we show that Fc g RIIIdependent responses are more intense in normal than in congenic mast cell–deficient Kit W /Kit W-v mice, indicating that Fc g RIII responses have mast cell–dependent and –independent components. Finally, we demonstrate that the upregulation of cell surface expression of Fc g RIII seen in Fc e RI a chain 2 / 2 mice corresponds to an increased association of Fc g RIII a chains with FcR b and g chains and is associated with enhanced Fc g RIII-dependent mast cell degranulation and systemic anaphylactic responses. Therefore, the phenotype of the Fc e RI a chain 2 / 2 mice suggests that expression of Fc e RI and Fc g RIII is limited by availability of the FcR b and g chains and that, in normal mice, changes in the expression of one receptor (Fc e RI) may influence the expression of functional responses dependent on the other (Fc g RIII). ( J. Clin. Invest. 1997. 99:915–925.)