IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis.
MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop lethal glomerulonephritis (GN) similar to human lupus nephritis, associated with the expression of lymphoproliferation gene lpr. To examine whether a particular IgG subclass is responsible for development of GN in these mice, first quantitative analysis of IgG subclasses in serum and in kidney eluates was performed. Although IgG2a was the dominant subclass in serum throughout the lifespan of mice, the IgG3 level in kidney eluates was three times higher than that of IgG2a at the 16 wk of age, which is the time of onset of development of severe GN. In sera of the 12-wk-old mice, half of the IgG3 was in immune complex form, whereas IgG2a in this form was only 17% of the total amount. Second, cyclosporin A, which ameliorates GN in MRL/lpr mice despite autoantibody production, was found to reduce serum IgG3 and mRNA levels, associated with the revision of cationic shift of the serum IgG3 spectrotype seen in isoelectric focusing. Third, among the hybrid mice with non-autoimmune-prone C3H/HeJ-lpr/lpr (C3H/lpr) mice, MRL/lpr x (MRL/lpr x C3H/lpr) F1, in which the genetic background for GN is likely segregated, the mRNA level for IgG3 correlated well with the degree of glomerular lesion. These findings indicate that production of IgG3 in MRL/lpr mice is one of the major factors responsible for development of GN in these mice, and that this is due to the genetic background of the MRL strain.
Takahashi
S
S
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Nose
M
M
Sasaki
J
J
Yamamoto
T
T
Kyogoku
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry; D015152:Blotting, Northern; D003524:Cyclosporins / Q000627:therapeutic use; D015870:Gene Expression; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000276:immunology; D008181:Lupus Nephritis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D003524:Cyclosporins; D007074:Immunoglobulin G; D012333:RNA, Messenger