Figure 1

Mechanisms of action for human B-cell activating factor and a proliferation-inducing ligand inhibitors. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) bind differently to the three receptors B-cell activating factor receptor (BAFF-R), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen (BCMA). Selective BAFF inhibitors block the interaction between soluble BAFF or both soluble and membrane BAFF and its receptors, leaving APRIL functions intact, whereas the dual BAFF/APRIL inhibitor atacicept (TACI-Ig) blocks the interaction of both BAFF and APRIL with all three receptors. BAFF inhibition depletes B cells and alters the selection of autoreactive B cells, and may have either direct or indirect effects on T cells and dendritic cells (DC).