Nephritogenicity and differential distribution of glomerular immune complexes related to immunogen charge

Nephritogenicity and the differential distribution of glomerular deposits as a function of immunogen charge were examined in a murine model of chronic active serum sickness. A range of differentially charged immunogens was used, i.e., chemically modified highly cationic or anionic bovine gamma-globulin (BGG), native unmodified isoelectrically focused slightly cationic or anionic BGG, and heterogeneous native BGG. The amounts and distribution of immune complexes in glomeruli were compared by immunofluorescence and electron microscopy 3 to 10 weeks after the initiation of 15 intravenous injections of the five immunogens and 13 days after intraperitoneal continuous release of the native unmodified BGGs by osmotic pumps. The results demonstrate that the more cationic the immunogen, the more nephritogenic and the greater the tendency to form subepithelial deposits in the glomerular basement membrane. The observed differences in nephritogenicity and localization induced by focused unmodified cationic and anionic fractions of BGG particularly emphasize immunogen charge as a major factor influencing glomerular distribution of immune complexes in this model. The findings indicate that several degrees of nephritogenicity and the differential distribution of immune complexes can be related to immunogen charge and strongly suggest that charge interactions may be of fundamental importance in the pathogenesis of immune complex glomerulonephritis.