Inactivated complement component 3b (iC3b)

Inactivated complement component 3b (iC3b) is a major cleavage product of complement component C3b, generated by factor I-mediated proteolysis with appropriate cofactors after complement activation. iC3b is a key opsonin that covalently attaches to pathogen surfaces or apoptotic cells and cannot form the complement convertase, thus halting amplification of the cascade. Its principal function is to mediate recognition and clearance by binding complement receptors—CR2 (CD21) on B cells, CR3 (CD11b/CD18) and CR4 (CD11c/CD18) on myeloid cells—promoting phagocytosis, modulating inflammation, and bridging innate and adaptive immunity. iC3b displays a unique, flexible structure with critical exposed domains (notably C3d and the remnant CUB domain) that facilitate receptor interaction. Its levels serve as biomarkers of complement activation, and its dysregulation is involved in autoimmunity, infection, and inflammatory disease pathogenesis. While there are no approved therapies directly targeting iC3b, modulating its generation or interaction with receptors is under investigation as a means to control pathological inflammation and immune complex diseases[1][2][4][5][6].

Other names

Inactivated C3bC3b inactivated by factor IC3b fragmentiC3b (commonly used in literature)

Mechanism of action involves inhibition of interaction with complement receptors (CR3, CR4, CR2), inhibition of complement activation and downstream opsonization/phagocytosis (by preventing generation or action of iC3b), and blockade of immune cell signaling mediated by iC3b-receptor engagement.