Factor B

Factor B is a component of the alternative pathway of complement. It contains a serine protease (SP) domain, and when activated it provides the catalytic activity of the alternative pathway C3 and C5 convertases. Factor B circulates as an inactive proenzyme (i.e., a zymogen), and only becomes activated after cleavage by the protein factor D. However, factor D can only cleave factor B when it is bound to the active forms of C3: C3(H2O) and C3b. Factor B is generated as a single-chain protein, and cleavage by factor D generates two peptide fragments (Ba and Bb). The Bb region (which contains the SP domain) remains bound to C3(H2O) and C3b, forming the alternative pathway convertases [C3(H2O)Bb and C3bBb]. As part of the C3 convertases, the SP domain of Bb has specific catalytic activity for cleavage of C3 molecules. The addition of another C3b molecule to the alternative pathway C3 convertase generates the C5 convertase (C3bBbC3b). As part of the alternative pathway C5 convertase, the SP domain of Bb cleaves C5 molecules, enabling the assembly of C5–C9 and the resultant formation of the membrane attack complex.