MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop
immune complex-mediated
glomerulonephritis,
granulomatous arteritis, and
thrombocytopenia. Recent genetic analyses in a few different strains of lupus-prone mice have pointed out a close correlation between
autoantibodies reactive with the endogenous retroviral env gene product, gp70, and the development and severity of
glomerulonephritis. We have also shown that
autoantibodies reactive with endogenous retroviral gp70 are closely correlated with the development of necrotizing polyarteritis in another lupus-prone strain of mice, SL/Ni. However, suggested pathogenicity of anti-gp70
autoantibodies has not yet been directly tested. To examine if anti-gp70
autoantibodies induce glomerular and vascular pathology, we established from unmanipulated MRL/lpr mice hybridoma clones that secrete
monoclonal antibodies reactive with endogenous xenotropic viral
env gene products. As reported separately, a high proportion of these anti-gp70 antibody-producing hybridoma clones induced in syngeneic non-autoimmune and
severe combined immunodeficiency mice proliferative or wire loop-like glomerular lesions with granular deposits of gp70,
IgG, and C3 in affected glomeruli. Some mice transplanted with these anti-gp70
autoantibody-producing hybridoma cells also showed massive subendothelial deposition of electron-dense materials in small arterioles in the kidneys. Furthermore, we identified an IgG2a-producing anti-gp70 hybridoma clone that induced microvascular intraluminal platelet aggregation,
thrombocytopenia, and amenia upon
transplantation into syngeneic non-autoimmune mice. This anti-gp70
autoantibody bound onto the surfaces of mouse platelets, and specifically precipitated a platelet
protein with an approximate relative molecular mass of 40000. Attachment of activated platelets to the intimal surfaces of small arteries was also observed by electron microscopy in mice transplanted with the pathogenic anti-gp70 IgG2a-producing hybridoma cells, suggesting an interaction between antibody-bound platelets and endothelial cells.