Activation and Inactivation of C3

ACTIVATION AND INACTIVATION OF C3

When C3b is inadvertently deposited on host cells containing cofactors for Factor I, C3b is rapidly cleaved into small products, which will not activate additional complement components. On the other hand, C3b molecules deposited on antigen are very slowly degraded by Factor I, allowing time for activation of the amplification loop and the MAC. Also, a prolonged presence of iC3b is observed on antigens. While iC3b has irreversibly lost the ability to participate in the complement activation sequence iC3b remains bound to the for-eign substance and enhances its phagocytosis.

Therefore, very important reactive sites become exposed when Factor I cleaves bound C3b. The newly exposed regions react with other cell receptors, CR2 and CR3. CR3, which avidly binds to iC3b, is not a ubiquitous complement receptor (like CR1), rather it is expressed on phagocytes and is very important in enhancing phagocytosis. However, even the site that reacts with CR3 is eventually lost as iC3b continues to be degraded by Factor I, which causes the iC3b to break into two major fragments: C3dg and soluble C3c. The C3dg fragment remains bound to the antigen and retains the site that interacts with CR2 (expressed by B cells and on follicular dendritic cells). With time, C3dg is further degraded into C3d by the continued action of plasma or tissue proteases; this fragment remains bound to the antigen and, like C3dg, continues to express the site for interaction with CR2.