Agalactosyl IgG and beta-1,4-galactosyltransferase gene expression in rheumatoid arthritis patients and in the arthritis-prone MRL lpr/lpr mouse.
Reduced galactosylation of immunoglobulin G (IgG) is well documented in rheumatoid arthritis (RA), but the reason for this defect is still unknown. There is some evidence supporting a defect in the biosynthetic pathway, and a reduction in the level of beta-1,4-galactosyltransferase (beta-1,4-GalTase) enzyme activity. Since glycosyltransferases are, in general, regulated at the level of transcription, we have measured the level of beta-1,4-GalTase gene expression in B cells from patients with RA and normal control individuals. We found no significant difference in mRNA levels for the transferase in these two groups (P > 0.7). MRL/Mp-lpr/lpr (MRL-lpr) mice develop a spontaneous arthritis with increased levels of agalactosyl IgG (G0). In spite of a significant reduction in the level of beta-1,4-GalTase mRNA in total spleen lymphocytes from MRL-lpr mice compared with the congenic MRL/Mp-(+/+) (MRL-(+/+) mice and with CBA/Ca mice, we found comparable levels of the beta-1,4-GalTase mRNA in purified B cells from both spleen and lymph nodes of the three strains. Amongst the lymphoid compartments examined, the spleen and peripheral blood were found to be the major contributors of G0 in MRL-lpr mice. These data indicate that in neither human RA, nor in an animal model of this disease, is reduced IgG galactosylation caused by impaired expression of the beta-1,4-GalTase gene in B lymphocytes. Furthermore, splenic B cells, which have normal levels of beta-1,4-GalTase mRNA, appear to be a major source of G0 in MRL-lpr mice.
Jeddi
P A
PA
Department of Immunology, University College London Medical School, UK.
Bodman-Smith
K B
KB
Lund
T
T
Lydyard
P M
PM
Mengle-Gaw
L
L
Isenberg
D A
DA
Youinou
P
P
Delves
P J
PJ
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009237:N-Acetyllactosamine Synthase / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology
D007074:Immunoglobulin G; D012333:RNA, Messenger; C064155:agalactosyl IGG; D009237:N-Acetyllactosamine Synthase