Figure 1. Formation and control of C3 at the cell surface. C3 is continuously activated by the alternative complement pathway and attaches to surfaces in the form of C3b in a random manner. When activation occurs, factor B (B) binds to C3b and is subsequently cleaved by factor D (D) into fragments Bb and Ba. The resulting C3 convertase (C3bBb) is stabilized by binding of properdin (P) and, in an amplification loop, generates more C3b molecules which deposit in the vicinity of the convertase. A powerful amplification reaction results in surface deposition of C3b (opsonization) and formation of C5 convertases, followed by the induction of the lytic complement pathway and cell lysis. Complement regulators existing in the fluid phase and on the cell membrane determine the fate of the newly formed C3b molecule. The activity is shown here for the fluid-phase regulators factor H and reconectin/FHL-1. These regulators either direct the dissociation of the C3/C5 convertases, or they inhibit the formation of these convertases by controlling factor B binding, i.e. decay-accelerating activity. In addition, they act as cofactors for factor I and cause the inactivation of the C3b protein to the inactive form iC3b.

Figure 2. Processing of C3 in the alternative pathway. A continuously and spontaneously formed C3 convertase cleaves plasma C3 to C3b and the anaphylactic C3a fragment. The thioester of C3b interacts with molecules in its vicinity and binds to cell surfaces. C3b is inactivated by factor I in combination with various cofactors in several steps. The first cleavage results in the inactive form of iC3b and the release of fragment C3f. A second cleavage liberates the large C3c fragment and leaves the smaller C3dg fragment attached to particles or biomolecules. Further cleavage forms the C3d fragment. The various fragments represent ligands for several C3-binding proteins and specific C3 receptors.