The influence of antibody functional affinity on the effector functions involved in the clearance of circulating immune complexes anti-BSA IgG/BSA.

A systematic study was carried out to investigate the role of antibody functional affinity in the capacity of immune complexes (IC) to activate the complement system and to trigger subsequently the molecular events involved in the handling of IC by providing a clearance mechanism. For this purpose, two populations of polyclonal anti-BSA IgG antibodies of different affinities were prepared, with values of 1.89x10(8) M(-1) and 4.94x10(8) M(-1). First we studied the capacity of IC formed at equivalence with both antibodies to activate the classical and the alternative pathways of human complement and the ability of the complexes to bind to erythrocyte C3b-C4b receptors (CR1; CD35). The data showed that the highest affinity antibodies were more efficient in activating complement by both pathways. However, their binding to erythrocyte CR1 was significantly lower compared to the binding of the lowest affinity IgG. Second we compared these IC in terms of their ability to stimulate the respiratory burst of neutrophils (PMN) and to induce the release of PMN lysosomal enzymes. In general, both of these PMN functions were better stimulated by the IC prepared with the IgG antibodies having a highest affinity, although the effects were variable for different IC concentrations. The suggestion to be drawn from the data is that the antibody affinity has an influence on the formation of the immune complex lattice, modulating its three-dimensional structure and the arrangement of the antibody Fc fragments, interfering with complement activation and access to the neutrophil IgG receptors. The significance of these observations for the understanding of how affinity influences the precise biological mechanism that participates in the fate of IC is discussed.