Clonal variations in complement activation and deposition of C3b and C4b on model immune complexes

This study examined the relationship between complement activation and the deposition of C3b and C4b on a panel of model immune complexes (IC). IC were constructed by combining murine monoclonal IgM, IgA, IgG1, IgG2a or IgG3 anti-dinitrophenyl (DNP) antibodies with DNP-bovine serum albumin (DNP-BSA). The IC were incubated with human plasma as a complement source and the formation of C4a and C3a, as well as the deposition of C4b and C3b on the IC, measured by radioimmunoassay. The results indicate that there were isotype-independent variations in the capacity of different types of IC to activate the classical pathway, especially for isotype-matched pairs of IC containing IgG1, IgG2a and IgG3 antibodies. In most cases, there was a direct relationship between classical pathway activation and the cleavage of C3. There was, for most of the IC, a direct correlation between cleavage of C4 and C3 and the subsequent deposition of C4b and C3b on the IC. However, a pair of IC constructed with independently derived IgG1 antibodies was virtually identical with respect to C3 cleavage and yet differed in the number of C3b molecules deposited on the IC. Collectively, these data suggest that the immunoglobulin variable region can play a significant role in both complement activation and the deposition of C3b and C4b on IC.