INTERACTIONS IN THE COMPLEMENT-MEDIATED LYSIS OF BLOOD GROUP-AB ERYTHROCYTES SENSITIZED SIMULTANEOUSLY WITH ANTI-A AND ANTI-B MONOCLONAL-ANTIBODIES

The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a Cr-51-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of Clq and C3 bound to sensitized red cells was measured by using purified, I-125-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and Clq binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more Clq than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of Clq to an antibody-sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization.