DISTINCT INTRACYTOPLASMIC SEQUENCES ARE REQUIRED FOR ENDOCYTOSIS AND PHAGOCYTOSIS VIA MURINE FC-GAMMA-RII IN MAST-CELLS

In the present work, we studied the phagocytic and endocytic properties of murine FcgammaRII in mast cells. Mouse mast cells express high-affinity receptors for monomeric IgE and three low-affinity receptors for complexed IgG: FcgammaRIIb1, FcgammaRIIb2, and FcgammaRIII. In previous studies we showed that, when aggregated by multivalent ligands, murine FcgammaRIIl, but not FcgammaRII, triggers the release of inflammatory mediators and cytokines by mast cells. Upon FcgammaR aggregation, mast cells not only release intracellular materials, they also internalize particulate and soluble immune complexes. We compared the ability of the two FcgammaRII isoforms to trigger phagocytosis and endocytosis in RBL-2H3 cells stably transfected with cDNAs encoding wild-type, deleted, and tyrosine mutant FcgammaRIIb1 or FcgammaRIIb2. We found that FcgammaRIIb2, but not FcgamaRIIb1, triggered both phagocytosis and endocytosis. We identified distinct intracytoplasmic sequences necessary for FcgammaRIIb2-mediated endocytosis and phagocytosis respectively, and we observed that two tyrosine residues, located in each of these sequences, are critical for endocytosis and/or phagocytosis. Our data indicate that the two internalization pathways diverge as early as signal transduction.