Complement receptor CR2 (CD21) is predominantly expressed on the surface of B-cells and follicular dendritic cells (FDCs). It binds the C3 fragments C3dg, C3d, and with lower affinity, inactive C3b (iC3b) on the antigen surface, where it forms the B cell co-receptor complex with CD19 and CD81 (Matsumoto et al. 1993). Co-ligation of receptors due to C3dg opsonisation lowers the threshold for B cell activation by 1000 to 10,000 times (Dempsey et al. 1996, Mongini et al. 1997); the C3d:CR2 complex induces an increase of B cell receptor (BCR) signaling in the presence of C3d-opsonized antigen on the B cell surface (Cherukuri et al. 2001). C3 is required for the induction and maintenance of B-cell lineage memory cells in germinal centers (GCs), where B cells encounter antigen-antibody-C3 fragment complexes on the surface of FDCs (Klaus & Humphrey 1986). C3d-opsonized antigen binds to CR2 on FDCs, which can present the antigen and induce effector and memory B cells (Fang et al. 1998).
Complement fragments, iC3b and C3dg, are produced in vivo due to the actions of the complement serine protease, factor I. This enzyme cleaves C3b in the presence of cofactors (factor H, MCP/CD46, complement receptor 1/CR1/CD35) to generate iC3b. CR1 acts as a cofactor for further factor I-mediated cleavage to C3dg.