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

IgA is the most abundant immunoglobulin in mucosal areas but is only the se cond most common antibody isotype in serum because it is catabolized faster than IgG, IgA exists in monomeric and polymeric forms that function throug h 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 i nterferon-gamma. To characterize gamma-less Fc alpha R functionally, we gen erated mast cell transfectants expressing wild-type human Fc alpha R or a r eceptor with a point mutation (Arg --> Leu at position 209) which was unabl e to associate with the gamma chain. Mutant gamma-less Fc alpha R bound mon omeric and polymeric human IgA1 or IgA2 but failed to induce exocytosis aft er receptor clustering. The two types of transfectant showed similar kineti cs of Fc alpha R-mediated endocytosis; however, the endocytosis pathways of the two types of receptor differed. Whereas mutant Fc alpha R were localiz ed mainly in early endosomes, those containing Fc alpha R-gamma 2 were foun d in endo-lysosomal compartments. Mutant gamma-less Fc alpha R recycled the internalized IgA toward the cell surface and protected against IgA degrada tion. Cells expressing the two forms of Fc alpha R, associated or unassocia ted with gamma chains, may thus have differential functions either by degra ding IgA antibody complexes or by recycling serum IgA.