[Role of immunoglobulins in the activation of complement]

Depending on their class and sub-class, immunoglobulins may activate the complement by the classical pathway or by the alternative pathway. This activating property depends on how immunoglobulins are associated. Activation by the classical pathway implies binding to, and activation of C1. Binding is essentially an ion type interaction between C1q and--in the case of human IgG's for instance--the C gamma 2 domain. It has recently been investigated in depth by various techniques, such as inhibition of the C1q--IgG interaction by chemical compounds or by peptides isolated from C gamma 2. Activation of C1 seems to involve some elements of C gamma 3. In addition to initiating the classical pathway, immunoglobulins may act as acceptors of the classical C3-convertase (C4b C2a); a structure accepting the newly formed C4b is present in the Fab portion of IgG. It would appear that optimal functioning of the complement system is achieved when the C1 activating site and the C3-convertase forming site are close together on the IgG molecule, since the newly born peptidic fragments have a very short life. Immunoglobulins may activate the alternative pathway via their Fab portion. This property is directly related to the ability of Ig's to accept nascent C3b, which probably includes that of accepting nascent C4b as described above. In the alternative pathway C3-convertase may form when structural conditions around IgG-bound C3b encourage binding of B to C3b rather than the intervention of I and H factors which degrade C3b. The Ig-C3b interaction responsible for activation of the alternative pathway may also be directly involved in solubilization of immune complexes during activation of complement.