Immune complexes with cationic antibodies deposit in glomeruli more effectively than cationic antibodies alone.
In previously published studies, highly cationized antibodies alone and in immune complexes bound to glomeruli by charge-charge interaction, but only immune complexes persisted in glomeruli. Because normal IgG does not deposit in glomeruli, studies were conducted to determine whether cationized antibodies can be prepared which deposit in glomeruli when bound to antigen but not when free in circulation. A series of cationized rabbit antiHSA was prepared with the number of added amino groups ranging from 13.3 to 60.2 per antibody molecule. Antibodies alone or in preformed soluble immune complexes, prepared at fivefold or 50-fold antigen excess, were administered to mice. With the injection of a fixed dose of 100 micrograms per mouse, antibodies alone did not deposit in glomeruli with less than 29.6 added amino groups by immunofluorescence microscopy. In contrast, 100 micrograms of antibodies with 23.5 added amino groups in immune complexes, made at fivefold antigen excess, formed immune deposits in glomeruli. With selected preparations of cationized, radiolabeled antibodies, deposition in glomeruli was quantified by isolation of mouse glomeruli. These quantitative data were in good agreement with the results of immunofluorescence microscopy. Immune complexes made at 50-fold antigen excess, containing only small-latticed immune complexes with no more than two antibody molecules per complex, deposited in glomeruli similar to antibodies alone. Selected cationized antibodies alone or in immune complexes were administered to mice in varying doses. In these experiments, glomerular deposition of immune complexes, made at fivefold antigen excess, was detected with five- to 10-fold smaller doses than the deposition of the same antibodies alone. These studies demonstrate that antibody molecules in immune complexes are more likely to deposit in glomeruli by charge-charge interactions than antibodies alone.
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D000936:Antigen-Antibody Complex / Q000032:analysis*; D002412:Cations / Q000032:analysis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis*; D007525:Isoelectric Focusing; D007678:Kidney Glomerulus / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits
D000906:Antibodies; D000936:Antigen-Antibody Complex; D002412:Cations; D007074:Immunoglobulin G