Role of antigenic charge and antibody avidity on the glomerular immune complex localization in serum sickness of mice

Abstract

Passive injection of mice with preformed immune complexes (IC) made from cationized bovine serum albumin (BSA) and anti-native BSA antibody gave immune deposits along the glomerular capillary walls at predominantly subepithelial sites, while similar quantities of complexes made with native, anionized BSA did not deposit. Peripheral localization could be obtained also using low avidity antibody and a great excess of native BSA. Ultracentrifugation analysis showed that the size of IC in the animals given complexes containing cationized BSA was a little larger than 7 S, whereas those formed with the native or anionized BSA were around 19 S. The anti-native BSA antibody had a low avidity for cationized BSA in vitro, and thus all the IC which could deposit peripheral capillary walls were small and contained low avidity antibody. Chemical cationization of BSA alters the precipitability of the antibody and also the size and stability of the complexes formed. In an active model, injection of cationized BSA into mice preimmunized with cationized BSA caused localization of the BSA and its antibody in the peripheral capillary walls. Analysis of the circulating IC formed in this model also revealed low avidity of antibody and small-sized IC. From these results, it is clear that chemical cationization of antigen changes the characteristics of the antigen-antibody interaction, e.g. low precipitating efficiency and the formation of small-sized IC. Therefore, in addition to interaction of cationized IC with the polyanion layer of the glomerular basement membrane (GBM), the properties of antigen-antibody interaction play an important role in the deposition of IC along the peripheral capillary walls in a model of membranous glomerulonephritis.