Capillary-localized low-affinity antibody-antigen complexes act as a focus for the deposition of high-affinity complexes.

The hypothesis that low-affinity antibody-antigen complexes localized in the glomerular capillary wall can act as a focus for the subsequent deposition of complexes containing high-affinity antibody was tested with three experimental systems: (1) Experimental zinc deficiency was used to modulate antibody affinity and to determine its effect on the development of glomerulonephritis. Low-affinity (LA) mice fed a zinc-containing diet (Zn+) produce low-affinity antibody and develop glomerulonephritis when injected daily with antigen. However, LA mice fed a zinc deficient diet (Zn-) produce high-affinity antibody and do not develop chronic glomerulonephritis. Furthermore, when LA mice fed on a Zn+ diet and given daily antigen injections for 25 days were then given a Zn- diet and 25 further daily antigen injections, they developed glomerulonephritis more severely than did control LA mice given Zn+ diet throughout the whole experiment; (2) Immune complex localization was induced in LA mice by daily injections of ovalbumin and then i.v. injection of preformed high affinity anti-DNP-DNP-HSA complexes. These localized in the glomerular capillary wall in ovalbumin-injected animals in contrast to their mesangial localization in controls; and (3) High-affinity mice (HA) were given injections of preformed high- or low-affinity anti-DNP-DNP-HSA complexes and then 50 daily injections of DNP-HSA. The localization of complexes in HA mice following daily antigen injection was markedly influenced by the immunochemical characteristics of the complexes initially injected. These results suggest that the capillary localization of small, low affinity antibody-containing antibody-antigen complexes acts as a focus for the subsequent localization of larger, high-affinity antibody-containing complexes.