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

Abstract

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) (FcαR) are expressed with or without the γ chain on monocytes and neutrophils. γ-less FcαR represent a significant fraction of surface FcαR molecules even on cells overexpressing the γ chain. The FcαR-γ2 association is up-regulated by phorbol esters and interferon-γ. To characterize γ-less FcαR functionally, we generated mast cell transfectants expressing wild-type human FcαR or a receptor with a point mutation (Arg → Leu at position 209) which was unable to associate with the γ chain. Mutant γ-less FcαR 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 FcαR-mediated endocytosis; however, the endocytosis pathways of the two types of receptor differed. Whereas mutant FcαR were localized mainly in early endosomes, those containing FcαR-γ2 were found in endo-lysosomal compartments. Mutant γ-less FcαR recycled the internalized IgA toward the cell surface and protected against IgA degradation. Cells expressing the two forms of FcαR, associated or unassociated with γ chains, may thus have differential functions either by degrading IgA antibody complexes or by recycling serum IgA.