C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I.

Abstract

We have prepared C3b covalently linked to IgG via a hydroxylamine-sensitive bond between the C3b alpha' chain and sites predominantly, but not exclusively, located in the IgG heavy chain. This C3b species displays relative resistance to inactivation by factors H and I when compared with free C3b. This resistance appears to be due entirely to reduced affinity of C3b-IgG for factor H. Resistance to inactivation is not conferred on C3b by binding to another serum glycoprotein of similar size, ceruloplasmin, and may be a special property of IgG. C3b-IgG demonstrates an enhanced capacity to consume serum C3 relative to C3b. These alterations of the behavior of C3b when bound to IgG may in part explain the augmentation of alternative pathway activity by IgG. In addition, IgG-induced protection of C3b might influence both complement-mediated killing and phagocytosis of bacteria, as well as modify the in vivo handling of IgG-containing soluble immune complexes.

Infectious diseases associated with complement deficiencies

“…The molecular basis for this effect is not clear, but carbohydrate moieties on the Fab portion of some IgG subclasses are apparently involved (55). In addition, surface-bound antibody can serve as a C3 acceptor, and C3bBb formed on IgG in this manner is relatively resistant to inactivation by control proteins (122,183). Hence, C3b deposited on IgG may be particularly effective in promoting the many functional activities of the complement cascade.…”

Membranoproliferative Glomerulonephritis Type II (Dense Deposit Disease)

“…Because IgG is the second most abundant protein in plasma and C3 has a weak affinity for IgG, during systemic activation of the complement cascade in the fluid phase, nascent C3b reacts predominantly with IgG to produce (C3b)2-IgG complexes (41). (C3b)2-IgG complexes are far better precursors of the C3 convertase of the AP than free C3b because in addition to being protected from inactivation by fH, they are intrinsically more potent than C3b in assembling a C3 convertase, presumably because they first bind properdin, which facilitates fB binding (42,43) (Figures 5 and 6). …”

Molecular basis for serum resistance in Neisseria gonorrhoeae

“…This suggests that events that transpire to create effective complement fixation may occur at the point of or before C3 fixation. The presence and quantity of bactericidal antibody are also important in this (4,16,25). The role of gonococcal activation of specific complement pathways has also been investigated.…”