C3D

C3d is a degradation product of the complement component C3, formed during activation of the complement system. It is a small fragment that can remain covalently attached to pathogen surfaces or immune complexes after C3b-derived processing, and it serves as a stable marker of complement activity in tissues and fluids.

Generation and structure: When C3 is cleaved by C3 convertases, C3b is generated and can attach to surfaces. Through subsequent proteolysis by the enzyme factor I in the presence of cofactors such as factor H, C3b is converted to iC3b and then further degraded to C3c and C3d. C3d remains bound to the surface more stably than some other fragments, often via residual covalent linkage, and can also be found in solution after release from the surface.

Biological function: C3d plays a key role in linking innate and adaptive immunity. It binds to the CD21 receptor (CR2) on B cells and follicular dendritic cells, enabling co-ligation of the B cell receptor with CD21. This lowers the threshold for B cell activation, promoting clonal expansion, germinal center formation, antibody production, and, in some contexts, class switching and affinity maturation. C3d’s interaction with CR2 is also exploited in vaccine research to enhance humoral responses.

Clinical and research relevance: C3d is used as an indicator of local or systemic complement activation and as a component in studies of immune complex processing. In vaccine design, fusion of antigens with C3d or C3d-like fragments can augment immunogenicity. Abnormal C3d generation or deposition can reflect dysregulated complement activity and may be involved in autoimmune or inflammatory conditions.

Overall, C3d functions as a molecular bridge between complement activation and adaptive humoral immunity, with applications in both basic research and clinical contexts.