Differential B lymphocyte galactosyltransferase activity in the MRL mouse model of rheumatoid arthritis.
Oligosaccharides can be of fundamental importance to glycoprotein function. Glycosylation abnormalities are present in rheumatoid arthritis (RA) and may be associated with disease pathogenesis. To determine whether similar disease mechanisms occur in the MRL-1pr/1pr autoimmune arthritic mouse, studies on B lymphocyte galactosyltransferase (GTase) have been carried out. In MRL mice, a significant reduction in peripheral blood lymphocyte (PBL) GTase activity was found when compared to their paired splenic (SP) GTase activity (-69%, p = 0.002) and histocompatible non-autoimmune control CBA/Ca mice (-67%; p = 0.002). The changes in PBL GTase activity are similar to those found in RA and on further analysis, using mixing experiments in the presence of purified human milk GTase, this reduction was shown not to be due to the presence of a soluble intracellular GTase inhibitor. Furthermore when examining MRL derived hybridoma cells producing IgG, significantly reduced GTase activity was detected in the rheumatoid factor (RF) producing hybridoma cells compared to those secreting an irrelevant antibody (-21%, p < 0.05). Together these findings suggest that the glycosylation changes observed in this study, and those reported previously in RA, are tissue-specific, may result from cells trafficking from centres of disease activity and are not the result of direct enzyme inhibition. It is now important to further understand the mechanisms controlling glycosylation and relate disease associated changes with those occurring as part of normal cellular physiology.
Axford
J S
JS
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London, UK.
Alavi
A
A
Bond
A
A
Hay
F C
FC
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D001402:B-Lymphocytes / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D005700:Galactosyltransferases / Q000378:metabolism*; D006031:Glycosylation; D006825:Hybridomas / Q000201:enzymology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology
D005700:Galactosyltransferases