Glomerulonephritis: the use of grafted hybridomas to investigate the role of epitope density, antibody affinity and antibody isotype in active serum sickness

Abstract

Two experimental models were used to investigate the role of antigen epitope density, antibody isotype and antibody affinity in immune-complex glomerulonephritis. In both models, two antigens were used: dinitrophenylated bovine serum albumin of high and low substitution ( DNP19BSA and DNP4BSA , respectively). In the first, acute actively induced model, a single intravenous injection of either of the two antigens was given to mice bearing hybridomas that secreted one of five monoclonal antibodies--four IgGl with varying affinities for the dinitrophenol hapten, and an IgM antibody with a similar affinity to that of the lowest affinity IgGl. The second, chronic actively induced model was similar, except that mice were immunosuppressed to reduce interference by the hosts' antibody responses and that 15 daily intraperitoneal injections of antigen were given. The immunofluorescent findings in both models were similar. Glomerular deposition of antibody and antigen in mice with high affinity IgG or low affinity IgM antibodies was mesangial when DNP4BSA or DNP19BSA was injected. However in mice with the lowest affinity IgG antibodies, deposition was extensive and predominantly capillary when DNP19BSA was injected but was minimal when DNP4BSA was injected. The relevance of these findings to the pathogenesis of glomerulonephritis is discussed.