INDUCTION OF DIFFERENT TYPES OF GLOMERULONEPHRITIS BY MONOCLONAL-ANTIBODIES DERIVED FROM AN MRL IPR LUPUS MOUSE

MRL/Mp-1pr/1pr(MRL/lpr) lupus mice develop glomerulonephritis in which the histopathological manifestations of the disease are characterized by diffuse cell-proliferative, crescentic, and/or wire loop-like lesi ons, resembling those of human lupus nephritis. Although these lesions are thought to be mediated by antibodies, little data is available to explain these regular variations in glomerular lesions induced by ant ibodies at the monoclonal level. We studied glomerular lesions of norm al or severe combined immunodeficient mice injected with nephritogenic immunoglobulin G3-producing hybridoma clones (2B11.3 and 7B68), which we previously established from an unmanipulated MRL/lpr mouse. Both c lones caused increased serum levels of immunoglobulin G3 with identica l patterns over time and both induced glomerular deposits of immunoglo bulin G3 and C3. However, 2B11.3 and 7B68 induced glomerular lesions t hat differed in their histopathological manifestations. The 2B11.3 clo ne generated cell-proliferative lesions associated with marked Mac-2-p ositive macrophage infiltrates, but the 7B68 clone induced lesions cha racterized by subendothelial hyaline deposits resembling wire loops. T he latter was not associated with significant inflammatory cell infilt rates at any point throughout the progression of the lesion. Thus, our findings suggest that the histopathological variation in glomerulonep hritis seen in MRL/lpr mice results from clonally expanded B cell clon es that produce nephritogenic antibodies with different pathogenic pot encies.