Carbohydrate-mediated clearance of antibody . antigen complexes from the circulation. The role of high mannose oligosaccharides in the hepatic uptake of IgM . antigen complexes.
After immunization of rats with bovine serum albumin (BSA) for a 12-day period, approximately 90% of anti-BSA antibody was IgM. The circulating half-life of limiting amounts of 125I-BSA in immunized and control rats was 6 min and 24 h, respectively. The rapid clearance of 125I-BSA was inhibited by pre- or co-injection of mannan and ovalbumin, but not by asialofetuin, rat serum albumin, carbon particles, dextran, or depletion of serum complement. Soluble IgM . 125I-BSA complexes, formed in vitro under conditions of antibody excess, were rapidly cleared from the circulation of nonimmunized rats, and clearance was also inhibited by ovalbumin but not by asialofetuin. Immune complexes formed in vivo or in vitro were recovered primarily (approximately 60% of dose) in hepatic nonparenchymal cells and in other organs of the reticuloendothelial system. In experiments in vitro, IgM was bound tightly by concanavalin A only when complexed with antigen. Digestion of IgM . 125I-BSA complexes with alpha-mannosidase abolished both binding by concanavalin A and rapid clearance in normal rats. These data suggest that antigen-induced conformational changes can result in exposure of high mannose oligosaccharides on IgM which signal the clearance of soluble immune complexes from the circulation.
D000818:Animals; D000936:Antigen-Antibody Complex; D001692:Biological Transport / Q000187:drug effects; D007075:Immunoglobulin M / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000276:immunology*; D008351:Mannans / Q000494:pharmacology; D008361:Mannosidases / Q000494:pharmacology; D009844:Oligosaccharides / Q000494:pharmacology*; D010047:Ovalbumin / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution
D000936:Antigen-Antibody Complex; D007075:Immunoglobulin M; D008351:Mannans; D009844:Oligosaccharides; D010047:Ovalbumin; D008361:Mannosidases