Studies in cobra venom factor treated rats of antibody coated erythrocyte clearance by the spleen: differential influence of red blood cell antigen number on the inhibitory effects of immune complexes on Fc dependent clearance.

The splenic component of the mononuclear phagocyte system (MPS) was investigated in decomplemented rats by determining the clearance from the blood of erythrocytes coated with a monoclonal antibody (R3/13). The infusion of immune complexes (IC), prepared at 10-fold antigen excess, at an appropriate time during the erythrocyte clearance produced a significant increase in the T1/2 of the antibody coated cells. Immune complexes formed with the F(ab')2 fragment of the rabbit antibody did not have any significant effect. A positive correlation was seen between the dose of immune complex infused and the degree of inhibition of erythrocyte clearance. The influence of red cell antigen number on the behaviour of erythrocytes sensitized with R3/13 was studied by comparing the clearance of DA and (DA X PVG) F1 erythrocytes. F1 erythrocytes, with only half the number of specific antigens on their surface that bind R3/13 antibody were cleared much more slowly (82 +/- 2.6 min, mean +/- s.e.) by the spleen than the DA erythrocytes (44 +/- 1.5 min P less than 0.001). Both cell suspensions were equally susceptible to inhibition by soluble IC. These studies show that the number of specific antigens on the red cell surface influences the rate at which sensitized cells are removed by splenic macrophage Fc receptors but not their susceptibility to inhibition by IC. Our results draw attention to a major defect in the use of autologous erythrocytes coated with anti-rhesus (D) immunoglobulin to assess macrophage Fc receptor function in man.