Two forms of the low-affinity Fc receptor for IgE differentially mediate endocytosis and phagocytosis: identification of the critical cytoplasmic domains.

We have previously identified two species of the low-affinity human Fc receptor for IgE, Fc epsilon RIIa and Fc epsilon RIIb, which differ only in a short stretch of amino acids at the N-terminal cytoplasmic end. Their differential expressions on B cells and monocytes suggest that Fc epsilon RIIa and Fc epsilon RIIb are involved in B-cell function and IgE-mediated immunity, respectively. Here we show that Fc epsilon RII-mediated endocytosis is observed only in Fc epsilon RIIa-expressing cells, whereas IgE-dependent phagocytosis is observed only in Fc epsilon RIIb-expressing cells, demonstrating the functional difference between Fc epsilon RIIa and Fc epsilon RIIb. Furthermore, site-directed mutagenesis revealed that the tyrosine residue in the Fc epsilon RIIa-specific region is important for endocytosis, and the Asn-Pro residues in the Fc epsilon RIIb-specific region are required for phagocytosis. These findings suggest that endocytosis and phagocytosis are functionally separable phenomena involving distinct amino acid residues.