The Immunological Significance of Antibody Affinity

Summary

Mice selectively bred to produce low affinity antibodies are more susceptible to immune complex glomerulonephritis induced by daily injections of a foreign protein antigen than are mice selected to produce high affinity antibody. Development of disease is associated with an inability to produce the normal maturational switch from low to high affinity antibody. Low affinity NM mice, selected by their failure to show affinity maturation after injection of adjuvantised antigen showed an even greater susceptibility to disease. Sucrose density gradient ultracentrifugation studies showed that immune complexes formed in high affinity mice were large (19 S) and cleared rapidly from the circulation. Immune complexes in low affinity mice were significantly smaller. We propose that immune complex diseases may result from an inherited or acquired form of immunodeficiency favouring a predominantly low affinity antibody response. Immune complexes formed from low affinity antibody have a tendency to dissociate and form small (12–17 S) complexes in antigen excess which may deposit in filtering membranes such as the renal glomerulus.