This research project was designed to gain insight into the pathogenesis of lupus nephritis and proteinuria. We use bacterial lipopolysaccharide (LPS) as a polyclonal activator of B cells in order to achieve acceleration of autoimmune disease and nephritis in three strains of mice (NZB/W, BXSB, and MRL/1). Although these strains of mice have in common features of lupus-like disease comparable to human systemic lupus erythematosus, they differ from each other in that the relative contribution of genetic, immunologic, environmental, and hormonal factors to disease expression vary. Thus, correlation of findings in several strains offers an opportunity to identify common pathogenetic and etiologic aspects of the disease. Our specific objectives are: 1. to study the immunomodulating effect of a polyclonal B cell activator on murine lupus nephritis, 2. to study binding and release of immune complexes from blood cells, and the influence of complement upon such binding and release, 3. to study the role of complement in the solubilization of immune complexes at various stages of lupus nephritis, 4. to study mononuclear phagocyte function through the clearance and uptake of soluble immune complexes at various stages of lupus nephritis, and 5. to study disease expression, serologic and morphologic changes, and alterations in glomerular permeability function at various stages of lupus nephritis in relation to items 1-4. Disease expression is assessed by a variety of immunopathologic, functional, and serologic assays of reactants believed to be of significance in the pathogenesis of lupus nephritis. Alterations in glomerular permeability function are assessed by quantitative and qualitative studies of proteins present in urine, by molecular probes of size- and charge-based barrier function, and by an ultrastructural search of morphologic correlates of increased glomerular permeability. Our efforts to understand dysfunction of the mononuclear phagocyte system and blood cell traffic of immune complexes, and the several pathways of complement interactions with immune complexes and cells should provide several insights into the role of immune complexes in the pathogenesis of inflammation and autoimmune diseases.