C5b6

C5b6 is an intermediate complex in the human complement system’s terminal pathway. It forms when the C5 convertase cleaves C5 to produce C5a and C5b, and the newly generated C5b quickly binds to the next component, C6, forming the C5b6 complex. In the absence of membranes, C5b6 is relatively unstable and does not by itself create pores.

As part of the assembly sequence leading to the membrane attack complex (MAC), C5b6 serves as a precursor that targets membranes. It can bind to C7 to produce C5b-7, which anchors into lipid bilayers. Subsequent recruitment of C8 and multiple C9 molecules completes MAC formation, creating transmembrane pores that can lyse susceptible cells and certain pathogens. The efficacy and localization of MAC activity are modulated by regulatory proteins on host cells, such as CD59, which inhibit final pore formation on human cells.

C5b6 is therefore a key early intermediate in the MAC pathway but is not itself cytolytic. Its stability and ability to associate with membranes determine the efficiency of MAC assembly. Deficiencies or dysfunctions in late complement components (C5–C9) increase susceptibility to infections with Neisseria species, reflecting MAC’s role in defending against certain bacteria. Therapeutically, inhibition of C5 activation (for example, by monoclonal antibodies) prevents formation of C5b and subsequent MAC assembly, reducing inflammatory damage in some diseases but raising the risk of meningococcal infections.