The effect on immunoglobulin glycosylation of altering in vivo production of immunoglobulin G

The effect on murine immunoglobulin G (IgG) glycosylation of altering IgG p roduction in vivo was assessed in interleukin (IL)-6 transgenic and CD4 kno ckout mice. C57BL/6 mice carrying the IL-6 transgene showed increased level s of circulating IgG. This was associated with decreased levels of galactos e on the IgG oligosaccharides. No decrease in beta 4-galactosyltransferase mRNA or in enzyme activity was seen in IL-6 transgenic mice. MRL-lpr/lpr mi ce normally have elevated levels of circulating IgG, again accompanied by d ecreased levels of IgG galactose. Disruption of the CD4 gene in MRL-lpr/lpr mice led to a substantial decrease in the concentration of circulating Igc , but IgG galactose levels remained low. Thus, an enforced decrease in IgG levels in the lymphoproliferative MRL-lpr/lpr mice did not alter the percen tage of agalactosyl IgG in these mice, suggesting that agalactosyl IgG prod uction is not simply caused by excessive IgG synthesis leading to an insuff icient transit time in the trans-Golgi, but rather to a molecular defect in the interaction between galactosyltransferase and the immunoglobulin heavy chain.