Abnormal IgG galactosylation in MRL-lpr/lpr mice: pathogenic role in the development of arthritis.
MRL-lpr/lpr (MRL/lpr) mice spontaneously develop arthritis by an increase in the incidence of agalactosylated oligosaccharides in serum IgG, similar to rheumatoid arthritis patients. However, whether this association has a pathogenic significance is still unknown. In this study, we analyzed the oligosaccharide structure of serum IgG in various MRL mice with or without arthritis, to clarify the relationship between the oligosaccharide abnormality and the development of arthritis. The level of agalactosylation in serum IgG was comparable in both arthritis-free MRL/lpr and MRL-+/+ (MRL/+) mice at 6 weeks of age. In contrast, the incidence of IgG lacking galactose markedly increased in MRL/lpr mice at 6 months of age (the age at which arthritis occurred), compared with that from age-matched MRL/+ mice without arthritis. However, the proportion of agalactosylated IgG increased similarly in anti-CD4 monoclonal antibody-treated MRL/lpr mice at 6 months of age, despite the absence of the development of arthritis, because of depletion of CD4+ T cells. These results suggest that the abnormality in IgG galactosylation of MRL/lpr mice developed in an age-dependent manner, but it did so independently of CD4+ T cell-dependent B-cell activation and is not a consequence of the development of arthritis.
Kuroda
Y
Y
Laboratory of Biomedical Research, Department of Applied Biochemistry, Tokai University, Hiratsuka, Japan.
Nakata
M
M
Hirose
S
S
Shirai
T
T
Iwamoto
M
M
Izui
S
S
Kojima
N
N
Mizuochi
T
T
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics / Q000628:therapy; D015704:CD4 Antigens / Q000276:immunology; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000032:analysis
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; C064155:agalactosyl IGG; D005690:Galactose