1. Inherited differences in the quantity and site of renal deposition of antigen were studied in two inbred strains of healthy rats, one of which, Lewis, is susceptible to Heymann's nephritis and the other (DA) is resistant.
2. Deposition of human cationic immunoglobulin G (IgG) was significantly less in the liver, spleen and kidneys of Lewis rats compared with DA rats, which suggests that the density of the negatively charged molecules in the capillary walls of Lewis rats is less than in DA rats. Immunofluorescent studies of the kidneys 15 min after administration of cationic IgG showed that it could be detected only on the glomerular basement membrane (GBM) and that the intensity of the deposits was less in Lewis rats.
3. The mesangial uptake of aggregated IgG was greater in DA rats at all times studied. There was remarkable similarity in the glomerular processing of cationic IgG and aggregated IgG in both strains.
4. These differences in glomerular properties, capillary charge and mesangial uptake may lead to differences in the deposition of antigen within the glomerulus and in the response to the subsequent inflammatory reactions. This provides a new hypothesis for genetic predisposition of individuals to particular glomerulopathies.