C3 convertase of the human alternative pathway of complement: modulation of enzyme activity and stability by mouse monoclonal antibodies to Bb

摘要

AbstractTo further characterize functional sites on C3b, Bb, the C3 convertase of the alternative pathway of complement, we examined the effect of four monoclonal antibodies on its activity and stability. These antibodies recognized antigenic epitopes on human Bb which were not fully exposed in intact factor B. Three of the monoclonal antibodies inhibited lysis of rabbit erythrocytes by normal human serum in the presence of Mg2+and EGTA. Two of these antibodies markedly inhibited the activity of purified C3b, Bb deposited on rabbit erythrocytes. However, all four monoclonal antibodies increased the half‐life of the C3 convertase. Thus, these results demonstrate that binding of antibodies to Bb may concomitantly stabilize C3b, Bb and abate its activity. It is likely that such antibodies induce in Bb conformational changes which increase the C3b, Bb complex stability but may also hinder its catalytic sit