Function and pathology of the sugar chains of human immunoglobulin G

Human immunoglobulin G (IgG) is unique among serum glycoproteins because it contains more than 30 different biantennary complex-type asparagine-linked oligosaccharides. This extremely high microheterogeneity is probably produced because human individuals have a series of B cell clones equipped with different sets of glycosyltransferases. Despite this complex composition, IgG samples purified from whole human sera have the same mole ratios of oligosaccharides, indicating that the ratio of B cell clones synthesizing IgGs with different sugar chains is constant in healthy individuals. We found that the glycosylation patterns of whole serum IgGs obtained from patients with rheumatoid arthritis (RA) are quite different from those of whole serum from healthy individuals. Structural studies of the oligosaccharides revealed that the sugar chains of the IgGs obtained from patients with RA are depleted of the beta-galactose residues. The sugar chains of transferrin from patients with RA are fully galactosylated. Therefore the galactose deletion from IgG is probably brought about by a decrease in galactosyltransferase activity in B cells rather than by degradation by galactosidase during circulation. Enzymic study revealed that human B cells contain various beta-galactosyltransferases which form the Gal(beta 1-4)GlcNAc groups in the sugar chains of different glycoproteins. Among these enzymes, abnormality in patients with RA was found only in the one that transfers beta-galactose residues specifically to degalactosylated IgG. This enzyme showed lower affinity toward UDP-Gal in B cells of patients with RA than that in healthy individuals.