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C3b is one of two components 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, and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or else forming 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 bond to the surface of invading pathogens. "Cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to -OH and -NH2 groups on foreign cell surfaces.[1]" This cleavage can occur via three mechanisms (classical pathway, alternative pathway and mannose binding lectin) that ultimately lead to the formation of a C3 convertase, which amplifies C3 cleavage on the surface of the microbial invader. The formation of C3 covertase functions as a positive feedback loop, as more C3b is cleaved, more C3 convertases are formed, further amplifying the signal. Once cleaved, C3b plays an important role in formation of the C3 and C5 convertases, as well as opsonization.

In the classical pathway, the microbial pathogen is coated in antibodies 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.

In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe is present, the C3b component will covalently bind to the surface of foreign invader. It then associates with Factor B, which is cleaved by Factor D into Factor Bb. This C3bBb convertase is stabilized by properdin (Factor P) preferentially on microbial surfaces over normal host surfaces, and is now able to cleave many more C3 molecules thus amplifying the signal. Incorporation of an additional C3b into the C3bBb C3 convertase leads to the formation of C3Bb3b 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 antigen's membrane. This pore disrupts the ionic and osmotic balance provided by the antigen's membrane, and leads to the death of the antigen cell.”

Once cleaved C3b can either generate C3 or C5 converstases, as mentioned above, or else covalently bind to the microbial surface, tagging the cell for phagocytosis in a process known as opsonization. Additionally, C3b molecules can attach to the Fc regions of antigen-bound antibodies leading to phagocytosis or movement to the liver with the C3b-tagged immune complex is then destroyed. In both cases C3b interacts with C3b receptors on phagocytic cells, such as complement receptor 1 (CR1) on macrophages, allowing for engulfment of the pathogen.

Due to the importance of C3b, disruptions resulting in deficiencies or up regulation of C3b generation can have serious implications for the health of a person. For example the uncontrolled cleavage of C3b is associated with the disease C3 glomerulopathy, in which deposits of C3 in the glomeruli disrupt kidney function and can eventually result in kidney failure.