Altered balance of inhibitory and active Fc gamma receptors in murine autoimmune glomerulonephritis.
Mag is an MRL-derived glomerulonephritis susceptibility locus that includes the Fcgr2b and Fcgr3 genes encoding the inhibitory Fc gamma receptor IIB (FcgammaRIIB) and active FcgammaRIII, respectively. We measured changes in gene balance in three B6.MRLc1 congenic mouse strains containing the 82-86, 92-100 and 100 cM regions of the MRL chromosome 1. We found that only the strain that has 92-100 (which includes Fcgr loci) developed glomerulonephritis. These congenic mice had splenomegaly, elevated blood urea nitrogen, anti-dsDNA antibodies and higher urinary albumin excretion compared to the parental strain C57BL/6(B6). Prior to the development of glomerulonephritis, large CD3- (T cell) and B220- (B cell) positive areas were identified in the spleens of B6.MRLc1(92-100) mice. Both Fc receptors were found in mesangial and dendritic cells; important sites of immune-complex clearance and antigen presentation. The FcgammaRIII-positive areas were more prominent in the congenic strain. Fcgr2b mRNA was lower in the B6.MRLc1(92-100) kidney and spleen than in those organs of the B6 mice while Fcgr3 expression and the Fcgr3 to Fcgr2b mRNA ratio was higher in the congenic strain kidneys, spleen and thymus than in those of the B6 prior to and at an early stage of glomerulonephritis. We conclude that the imbalance of inhibitory and active Fc gamma receptors influences the pathogenesis of glomerulonephritis.
Ichii
Osamu
O
1Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Konno
Akihiro
A
Sasaki
Nobuya
N
Endoh
Daiji
D
Hashimoto
Yoshiharu
Y
Kon
Yasuhiro
Y
D000818:Animals; D001327:Autoimmune Diseases; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis* / Q000235:genetics
C499172:Fcgr2b protein, mouse; C485700:Fcgr3 protein, mouse; D012333:RNA, Messenger; D017452:Receptors, IgG