Structure and function of the human C3b receptor.

The human C3b receptor (C3bR) is a glycoprotein that exists in two allotypic forms having Mr values of approximately 250,000 (F) and 260,000 (S). The number of receptors present on erythrocytes varies by eightfold among normal individuals and is genetically regulated by two codominant alleles that are distinct from the alleles determining the structural polymorphism. C5a and C5ades Arg induce rapid increases in the number of receptors expressed by neutrophils in vitro, and probably account for the increased receptor expression on neutrophils in patients undergoing hemodialysis. Cytoskeletal association of the C3bR on monocytes and neutrophils is suggested by experiments demonstrating receptor-mediated phagocytosis and adsorptive endocytosis through coated pits, and by the reciprocal coredistribution of cross-linked C3b and Fc receptors and the detergent insolubility of cross-linked C3bR. The factor H-like cofactor activity of the C3bR promotes the cleavage of bound C3b to iC3b, C3c, and C3d,g, which may enhance the clearance of circulating immune complexes and the generation of ligands for CR2 and CR3. The inherited partial deficiency of the erythrocyte C3bR in patients with systemic lupus erythematosus and the absence of glomerular C3bR in these patients with proliferative glomerulonephritis may contribute to systemic and organ-specific abnormalities in the clearance of immune complexes in this disease.