The role of immune complexes in the activation of the first component of human complement.
Immune complex-induced C1 activation and fluid phase C1 autoactivation have been compared in order to elucidate the immune complex role in the C1 activation process. Kinetic analyses revealed that immune complex-bound C1 activates seven times faster than fluid phase C1 spontaneously activates. The rate of spontaneous C1 activation increased after decreasing the solution ionic strength. In fact at one-half physiologic ionic strength (i.e., 0.08 M), the kinetics of spontaneous C1 activation were indistinguishable from the kinetics of activation of immune complex-bound C1 at physiologic ionic strength. The enhanced fluid phase C1 activation at low ionic strength resulted neither from C1 nor C1q aggregation, nor from selective effects on the C1r2S2 subunit; however, at the reduced ionic strength, the C1 association constant (defined for C1q + C1r2S2 in equilibrium C1qr2S2) did increase to 2.3 X 10(8) M-1, which is equal to that for C1 bound to an immune complex at physiologic ionic strength. Therefore, C1 can spontaneously activate in the fluid phase as rapidly as C1 on an immune complex when the strength of interaction between C1q and C1r2S2 is the same in both systems. In conclusion, under physiologic conditions, C1q and C1r2S2 are two weakly interacting proteins. Immune complexes provide a site for the assembly of a stable C1 complex, in which C1q and C1r2S2 remain associated long enough for C1q to activate C1r2S2. Thus, immune complexes enhance the intrinsic C1 autoactivation process by strengthening the association of C1q with C1r2S2.
D000936:Antigen-Antibody Complex / Q000378:metabolism / Q000502:physiology*; D002499:Centrifugation, Density Gradient; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003166:Complement Activating Enzymes / Q000378:metabolism; D003167:Complement Activation; D003172:Complement C1 / Q000276:immunology* / Q000378:metabolism; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s; D003171:Complement Pathway, Classical; D006801:Humans; D007700:Kinetics; D009994:Osmolar Concentration
D000936:Antigen-Antibody Complex; D003172:Complement C1; D015922:Complement C1q; D003166:Complement Activating Enzymes; D015923:Complement C1r; D003173:Complement C1s