IgA-mediated elimination of antigens by the hepatobiliary route

Polymeric IgA antibody mediates the transport of corresponding antigens, in the form of IgA immune complexes (IC), from the circulation into the bile, whereas monomeric IgA, IgG, and IgM are ineffective. Transport has been shown with dinitrophenyl albumin and bacterial polysaccharides such as pneumococcal SIII and C-substance. The process does not result in breakdown of the antigen, which can be detected in the bile in intact free and IgA-bound forms. Although IgG promotes clearance of antigen from the circulation mainly to the liver, only low levels of breakdown fragments are detectable in bile. In mice, the mechanism of IgA IC transport does not appear to involve Kupffer cells, the complement system, or the glycoprotein receptors on liver cells because attempts to block these systems failed to affect transport. The mechanism appears to be analogous to that for free IgA. Transport could be inhibited by antigen-nonspecific IgA, but not IgG or IgM. IgA IC were found in the bile but not in the saliva, milk, urine, or bronchial or intestinal washings. A similar pattern of appearance was seen when IgA alone was injected. Thus hepatobiliary transport appears to be the major pathway for the clearance of both IgA IC and free IgA from the circulation.