Alternative endocytic pathway for immunoglobulin A Fc receptors (CD89) depends on the lack of FcRγ association and protects against degradation of bound ligand

IgA is the most abundant immunoglobulin in mucosal areas but is only the second most common antibody isotype in serum because it is catabolized faster than IgG, IgA exists in monomeric and polymeric forms that function through receptors expressed on effector cells. Here, we show that IgA Fc receptor(s) (Fc alpha R) are expressed with or without the gamma chain on monocytes and neutrophils, gamma-less Fc alpha R represent a significant fraction of surface Fc alpha R molecules even on cells overexpressing the gamma chain. The Fc alpha R-gamma 2 association is up-regulated by phorbol esters and interferon-gamma. To characterize gamma-less Fc alpha R functionally, we generated mast cell transfectants expressing wild-type human Fc alpha R or a receptor with a point mutation (Arg --> Leu at position 209) which was unable to associate with the gamma chain. Mutant gamma-less Fc alpha R bound monomeric and polymeric human IgA1 or IgA2 but failed to induce exocytosis after receptor clustering. The two types of transfectant showed similar kinetics of Fc alpha R-mediated endocytosis; however, the endocytosis pathways of the two types of receptor differed. Whereas mutant Fc alpha R were localized mainly in early endosomes, those containing Fc alpha R-gamma 2 were found in endo-lysosomal compartments. Mutant gamma-less Fc alpha R recycled the internalized IgA toward the cell surface and protected against IgA degradation. Cells expressing the two forms of Fc alpha R, associated or unassociated with gamma chains, may thus have differential functions either by degrading IgA antibody complexes or by recycling serum IgA.