IDENTIFICATION OF THE LOW AFFINITY RECEPTOR FOR IMMUNOGLOBULIN-E ON MOUSE MAST-CELLS AND MACROPHAGES AS FC-GAMMA-RII AND FC-GAMMA-RIII

In addition to their well characterized high affinity immunoglobulin E (IgE) receptors (Fc-epsilon-RI) mast cells have long been suspected to express undefined Fc receptors capable of binding IgE with low affinity. In this paper, we show that Fc-gamma-RII and Fc-gamma-RIII, but not Mac-2, on mouse mast cells and macrophages bind IgE-immune complexes. This binding is efficiently competed by 2.4G2, a monoclonal antibody against the extracellular homologous region of both Fc-gamma-RII and Fc-gamma-RIII. Furthermore, IgE-immune complexes bind specifically to Fc-gamma-RII or Fc-gamma-RIII transfected into COS-7 cells. The association constants of IgE binding estimated from competition experiments are about 3.1 x 10(5) M-1 for Fc-gamma-RII, and 4.8 x 10(5) M-1 for Fc-gamma-RIII. Engagement of Fc-gamma-RII and Fc-gamma-RIII with IgE-immune complexes (after blocking access to Fc-epsilon-RI) or with IgG-immune complexes triggers C57.1 mouse mast cells to release serotonin. This release is inhibited by 2.4G2, and at maximum, reaches 30-40% of the intracellular content, about half of the maximal release (60-80%) obtained after Fc-epsilon-RI engagement. These data demonstrate that mouse Fc-gamma-RII and Fc-gamma-RIII are not isotype specific, and that the binding of IgE-immune complexes to these receptors induces cell activation.