The effect on immunoglobulin glycosylation of altering in vivo production of immunoglobulin G.
The effect on murine immunoglobulin G (IgG) glycosylation of altering IgG production in vivo was assessed in interleukin (IL)-6 transgenic and CD4 knockout mice. C57BL/6 mice carrying the IL-6 transgene showed increased levels of circulating IgG. This was associated with decreased levels of galactose on the IgG oligosaccharides. No decrease in beta4-galactosyltransferase mRNA or in enzyme activity was seen in IL-6 transgenic mice. MRL-lpr/lpr mice normally have elevated levels of circulating IgG, again accompanied by decreased levels of IgG galactose. Disruption of the CD4 gene in MRL-lpr/lpr mice led to a substantial decrease in the concentration of circulating IgG, but IgG galactose levels remained low. Thus, an enforced decrease in IgG levels in the lymphoproliferative MRL-lpr/lpr mice did not alter the percentage of agalactosyl IgG in these mice, suggesting that agalactosyl IgG production is not simply caused by excessive IgG synthesis leading to an insufficient transit time in the trans-Golgi, but rather to a molecular defect in the interaction between galactosyltransferase and the immunoglobulin heavy chain.
Jeddi
P
P
Department of Immunology, University College London, UK.
Keusch
J
J
Lydyard
P M
PM
Bodman-Smith
K B
KB
Chesnutt
M S
MS
Wofsy
D
D
Hirota
H
H
Taga
T
T
Delves
P J
PJ
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics*; D005690:Galactose / Q000378:metabolism; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics*; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000201:enzymology / Q000276:immunology
D015704:CD4 Antigens; D007074:Immunoglobulin G; D015850:Interleukin-6; D005700:Galactosyltransferases; D005690:Galactose