AGALACTOSYL IGG AND BETA-1,4-GALACTOSYLTRANSFERASE GENE-EXPRESSION INRHEUMATOID-ARTHRITIS PATIENTS AND IN THE ARTHRITIS-PRONE MRL LPR LPR MOUSE/

Reduced galactosylation of immunoglobulin G (IgG) is well documented i n rheumatoid arthritis (RA), but the reason for this defect is still u nknown. There is some evidence supporting a defect in the biosynthetic pathway, and a reduction in the level of beta-1,4-galactosyltransfera se (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 patient s with RA and normal control individuals. We found no significant diff erence 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 in creased levels of agalactosyl IgG (G0). In spite of a significant redu ction in the level of p-1,4-GalTase mRNA in total spleen lymphocytes f rom 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-GalTa se mRNA in purified B cells from both spleen and lymph nodes of the th ree strains. Amongst the lymphoid compartments examined, the spleen an d peripheral blood were found to be the major contributors of G0 in MR L-lpr mice. These data indicate that in neither human RA, nor in an an imal model of this disease, is reduced IgG galactosylation caused by i mpaired expression of the beta-1,4-GalTase gene in B lymphocytes. Furt hermore, 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.