Retroviral gp70 immune complexes in NZB x NZW F2 mice with murine lupus nephritis.

Abstract

NZB x NZW (NZB x W) F1 hybrid mice spontaneously develop a disease most prominently characterized by immune complex glomerulonephritis (GN), which seems to be associated with both antibodies to DNA and to the serum retroviral envelope glycoprotein, gp70. To evaluate the contribution of each of these autoimmune responses to the pathogenesis of the GN, we studied NZB x W F2 mice in which the two responses appeared to segregate relatively independently. Use of this model permitted analysis of possible correlations between each response and the G.N. The presence of circulating anti-gp 70-complexed gp70 correlated significantly with the development of fatal GN and one could predict the course of renal disease by computing the rising serum levels of gp70 complexed with antibodies. In contrast, the presence of free antibodies to either double-stranded or single-stranded DNA was not significantly associated with the development of fatal GN. This association of anti-gp70 antibody production with these animals' early death from GN strongly suggests that the gene(s) governing production of antibodies to serum retroviral gp70 may be one of the major genes responsible for spontaneous renal disease segregated in NZB x W F2 generations.

Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production

“…In fact, non-Yaa and Yaa B6.bcl-2 Tg males displayed neither measurable levels of gp70-anti-gp70 IC ( X 0.1 ? g/ml), implicated in mouse lupus nephritis [24,25] (Table 1). Nevertheless, more than one third of B cells were still derived from BXSB mice.…”

Genetic Control of Glycoprotein 70 Autoantigen Production and Its Influence on Immune Complex Levels and Nephritis in Murine Lupus

“…These mice spontaneously develop an autoimmune disease characterized by the production of IgG autoantibodies and the development of a severe immune complex-mediated glomerulonephritis. The major targets of autoantibodies are chromatin constituents (DNA and histones) and the endogenous retroviral glycoproteins, gp70 (1)(2)(3)(4)(5)(6). Both anti-chromatin and anti-gp70 autoantibodies, measured as gp70-anti-gp70 immune complexes (gp70 IC), have been implicated in the development of the progressive lupus nephritis in (NZB ϫ NZW)F 1 mice (5,(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

The Sgp3 Locus on Mouse Chromosome 13 Regulates Nephritogenic gp70 Autoantigen Expression and Predisposes to Autoimmunity

“…The development of a fatal immune complex-mediated glomerulonephritis (GN) 3 is closely associated with the appearance of elevated serum levels of IgG Abs with reactivities against nuclear Ags. Sera from these strains also contain Abs directed against endogenous retroviral envelope gp70 in the form of gp70-anti-gp70 immune complexes (gp70 IC) that appear with onset of the disease and increase throughout its course (2).…”

“…Sera from these strains also contain Abs directed against endogenous retroviral envelope gp70 in the form of gp70-anti-gp70 immune complexes (gp70 IC) that appear with onset of the disease and increase throughout its course (2). In several genetic studies of murine lupus, levels of serum gp70 IC were shown to best correlate with development of severe GN (3)(4)(5)(6)(7)(8). Recently, the critical importance of gp70 IC formation in disease pathology was more directly demonstrated by induction of glomerular lesions and gp70 deposition in nonautoimmune mice after transfer of anti-gp70 mAbs derived from MRL-Fas lpr (9).…”