C5b

C5b is a fragment of the complement component C5 produced during activation of the complement system. It originates when the C5 convertase enzyme cleaves C5 into C5a and C5b. C5b is unstable on its own and rapidly participates in the assembly of the membrane attack complex (MAC).

C5b binds to C6, forming C5b-6, which then recruits C7, C8, and C9 to assemble the holocomplex C5b-9 MAC. The MAC inserts into target cell membranes, creating pores that disrupt osmotic integrity and can cause cell lysis. MAC formation is particularly effective against certain bacteria and is a key effector mechanism of the terminal complement pathway.

Regulation and host protection: To prevent damage to host tissues, cells express regulatory proteins such as CD59 (protectin), which blocks C9 polymerization, and soluble proteins like vitronectin and clusterin that deter MAC assembly in circulation. Upstream regulators (e.g., CD55, CD46, Factor I) limit generation of C3 and C5 convertases to minimize MAC formation.

Clinical relevance: Inherited or acquired defects in MAC regulation can lead to disease; for example, deficiency of CD55 or CD59 causes increased susceptibility to complement-mediated lysis, as seen in paroxysmal nocturnal hemoglobinuria. Therapeutics that inhibit C5 cleavage, such as eculizumab and ravulizumab, reduce C5a and C5b formation and MAC assembly, and are used to treat certain complement-mediated disorders.