C3b

C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound to C4b and C2a (C4b2a3b complex) or when an additional C3b molecule binds to the C3bBb complex (C3bBb3b complex).

C3b's ability to perform these important functions derives from its ability to covalently bind to the surface of invading pathogens within an organism's body. The cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to hydroxyl (-OH) and amine (-NH2) groups on foreign cell surfaces.

This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation of a C3 convertase functions as a positive feedback loop, so as more C3b is cleaved, more C3 convertases are formed, further amplifying the signal on the surface the microbial invader. This amplification of signal serves as a powerful tool for the immune system in effective clearance of the invading pathogen.

In the classical pathway, the microbial pathogen is coated in antibodies (IgG and IgM) released by B cells. The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 complex cleaves C4 and C2 forming a C4bC2a complex that covalently bonds to the surface of the microbe and functions as a C3 convertase, binding and cleaving C3 into C3a and C3b. Binding of a C3b molecule to the C4bC2a complex (C4b2a3b) results in the formation of a C5 convertase, which cleaves C5 into C5a and C5b. C5b associates with C6, C7, C8, and C9, all of which form a complex that results in a pore through the pathogen's membrane. This pore disrupts the ionic and osmotic balance provided by the pathogen's membrane, and leads to the death of the pathogen cell.

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