IgG is associated with the asialoglycoprotein receptor in the human liver

Various pathophysiological relationships between IgA and the asialoglycoprotein receptor on hepatocytes have been proposed. As a step toward defining these relationships, we purified the receptor from human livers by means of p-aminophenyl beta-D-thiogalactopyranoside-agarose affinity chromatography. Unexpectedly, we found the asialoglycoprotein receptor to be associated specifically with IgG. Evidence for the specific association included the following: (a) IgG, but little IgA or IgM, was associated with asialoglycoprotein receptor that had been bound to asialoorosomucoid in an enzyme-linked immunosorbent assay; (b) the asialoglycoprotein receptor-associated IgG was predominantly IgG2 and IgG4 subclasses, whereas serum IgG is predominantly IgG1; and (c) some asialoglycoprotein receptor was specifically recovered together with IgG from an anti-IgG affinity column. The association of IgG with asialoglycoprotein receptor was not mediated by receptor recognition of carbohydrate moieties because IgG neither bound directly to asialoglycoprotein receptor nor inhibited binding of asialoglycoprotein receptor to asialoorosomucoid in vitro. The association could not be attributed to antigen-antibody interaction either. We conclude that IgG is associated in vitro with the asialoglycoprotein receptor by a mechanism not yet fully defined and speculate that the IgG serves an immunological function.