Cm. Marzocchi-machado et al., The influence of antibody functional affinity on the effector functions involved in the clearance of circulating immune complexes anti-BSA IgG BSA, IMMUNOL INV, 28(2-3), 1999, pp. 89-101
A systematic study was carried out to investigate the role of antibody func
tional affinity in the capacity of immune complexes (IC) to activate the co
mplement system and to trigger subsequently the molecular events involved i
n the handling of IC by providing a clearance mechanism. For this purpose,
two populations of polyclonal anti-BSA IgG antibodies of different affiniti
es were prepared, with values of 1.89x10(8) M-1 and 4.94x10(8) M-1. First w
e 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 eff
icient in activating complement by both pathways. However, their binding to
erythrocyte CR1 was significantly lower Compared to the binding of the low
est affinity IgG. Second we compared these IC in terms of their ability to
stimulate the respiratory burst of neutrophils (PMN) and to induce the rele
ase of PMN lysosomal enzymes. In general, both of these PMN functions were
better stimulated by the IC prepared with the IgG antibodies having a highe
st affinity, although the effects were variable for different IC concentrat
ions. The suggestion to be drawn from the data is that the antibody affinit
y has an influence on the formation of the immune complex lattice, modulati
ng its three-dimensional structure and the arrangement of the antibody Fc f
ragments, interfering with complement activation and access to the neutroph
il IgG receptors. The significance of these observations for the understand
ing of how affinity influences the precise biological mechanism that partic
ipates in the fate of IC is discussed.