C3b

C3b is a fragment of the complement component C3 generated during activation of the complement system. It is produced when C3 is cleaved by C3 convertases, yielding C3a and C3b. The thioester in C3b allows it to covalently attach to nearby surfaces, marking pathogens or damaged cells for immune attack.

As an opsonin, surface-bound C3b promotes phagocytosis by macrophages and neutrophils via complement receptor CR1 (CD35) and related receptors. C3b also participates in the formation of C5 convertases: in the alternative pathway, C3b binds to C3bBb to form C5 convertase C3bBb3b; in the classical and lectin pathways, C4b2a3b acts as the C5 convertase. These complexes cleave C5 into C5a and C5b, with C5b initiating the assembly of the membrane attack complex (MAC) involving C6 through C9.

Regulation and inactivation are essential to prevent host injury. Factor I, with cofactors such as factor H (fluid phase and surfaces) or MCP (CD46), cleaves C3b to iC3b and then to C3d, reducing activity.Decay-accelerating factor (DAF/CD55) promotes decay of C3 and C5 convertases, while CR1 (CD35) assists in clearance of opsonized material. iC3b remains an opsonin for CR3 and CR4, whereas C3d binds CR2 (CD21) on B cells and can enhance antibody responses.

Clinical relevance: C3b is central to both innate and adaptive immunity, linking pathogen opsonization to phagocytosis and antibody production. Dysregulation of C3b generation or regulation is associated with autoimmune and inflammatory diseases, such as atypical hemolytic uremic syndrome and age-related macular degeneration. Therapeutic strategies may target C3b generation or regulatory pathways.