C3 Cleaved by Membrane Proteases Binds to C3b Acceptors Expressed on Concanavalin A‐Stimulated Human Lymphocytes and Enhances Antibody‐Dependent Cellular Cytotoxicity

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Abstract
On activation of cells membrane‐associated proteases—including serine esterases known to cleave the third component of complement (C3)—become expressed. In this paper it is shown that as a consequence of this enzyme activity isolated native human C3 added to concanavalin A (Con A)‐activated human lymphocytes is cleaved on the surface of the blast cell. This enables the immediate fixation of nascent C3b (C3bx) through its short‐lived metastable biinliniisite to Oh acceptors (C3bA's) newly expressed on Con A‐stimulaled cells. Aeceptor‐bound C3b is detected by the immune adherence rosette formation of the O‐treated Con A blasts with the C3b receptor (C3bR)‐bearing O. Rh+ erythroeytes (32 ± 4%). The cleavage of C3 and the covalent fixation of C3b are shown to he inhibited hy phenylmethylsulphonyl fluoride and methylamine, respeclively. As a functional consequence of the covalent fixation of C3b to the mitogen‐activatcd lymphocytes it is demonstrated that the antibody‐dependent cellular cytotoxicity (ADCC) of these cells against O. Rh erythrocytes sensitized with anti‐D IgG is significantly enhanced. The C3 specificity of the process and the role of C3bR's of the target cells: are proved. It is postulated that effector cell‐bound C3b amplifies ADCC by improving effector cell‐target cell contact.