Establishment of monoclonal anti-retroviral gp70 autoantibodies from MRL/lpr lupus mice and induction of glomerular gp70 deposition and pathology by transfer into non-autoimmune mice

Several strains of mice, including MRL/MpJ mice homozygous for the Fas muta nt lpr gene (MRL/lpr mice), F-1 hybrids of New Zealand Black and New Zealan d White mice, and BXSB/MpJ mice carrying a Y-linked autoimmune acceleration gene, spontaneously develop immune complex-mediated glomerulonephritis. Th e involvement of the envelope glycoprotein gp70 of an endogenous xenotropic virus in the formation of circulating immune complexes and their depositio n in the glomerular lesions have been demonstrated, as has the pathogenicit y of various antinuclear, antiphospholipid, and rheumatoid factor autoantib odies. In recent genetic linkage studies as well as in a study of cytokine- induced protection against nephritis development, the strongest association of serum levels of gp70-anti-gp70 immune complexes, rather than the levels of antinuclear autoantibodies, with the development and severity of glomer ulonephritis has been demonstrated, suggesting a major pathogenic role of a nti-gp70 autoantibodies in the lupus-prone mice, However, the pathogenicity of anti-gp70 autoantibodies has not yet been directly tested. To examine i f anti-gp70 autoantibodies induce glomerular pathology, we established from unmanipulated MRL/lpr mice hybridoma clones that secrete monoclonal antibo dies reactive with endogenous xenotropic viral Env gene products. Upon tran splantation, a high proportion of these anti-gp70 antibody-producing hybrid oma clones induced in syngeneic non-autoimmune and severe combined immunode ficiency mice proliferative or wire loop-like glomerular lesions. Furthermo re, deposition of gp70 in glomeruli and pathological changes were observed after intravenous injection of representative clones of purified anti-gp70 immunoglobulin G, demonstrating pathogenicity of at least some anti-gp70 au toantibodies.