Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation.
C1q-deficient (C1qa-/-) mice develop antinuclear Abs and glomerulonephritis (GN) characterized by multiple apoptotic bodies. To explore the contribution of C3 activation to the induction of spontaneous GN, C1qa-/- mice were crossed with factor B- and C2-deficient (H2-Bf/C2-/-) mice. GN was present in 64% of the 45 C1qa/H2-Bf/C2-/- mice compared with 8% of the 65 H2-Bf/C2-/- mice and none of the 24 wild-type controls. IgG was detected in the glomeruli of diseased C1qa/H2-Bf/C2-/- kidneys. However, glomerular staining for C3 was absent. Increased numbers of glomerular apoptotic bodies were detected in undiseased C1qa/H2-Bf/C2-/- kidneys. These findings support the hypothesis that C1q may play a role in the clearance of apoptotic cells without the necessity for C3 activation and demonstrate that the activation of C3 is not essential for the development of GN in this spontaneous model of lupus-like disease.
Mitchell
D A
DA
Rheumatology Section and Department of Histopathology, Hammersmith Campus, Imperial College School of Medicine, London, United Kingdom.
Taylor
P R
PR
Cook
H T
HT
Moss
J
J
Bygrave
A E
AE
Walport
M J
MJ
Botto
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D003167:Complement Activation / Q000235:genetics*; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics; D003175:Complement C2 / Q000172:deficiency / Q000235:genetics; D003176:Complement C3 / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000235:genetics; D003171:Complement Pathway, Classical / Q000235:genetics; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains
D000974:Antibodies, Antinuclear; D003175:Complement C2; D003176:Complement C3; D015922:Complement C1q