BAFF / APRIL

Class

Fusion protein (TACI-Fc, dual BAFF/APRIL inhibitor)

Pathway

B-cell survival signaling (BAFF/APRIL pathway)

BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) are signaling proteins belonging to the tumor necrosis factor family that support the survival, maturation, and antibody production of B lymphocytes, the immune cells responsible for producing antibodies. In autoimmune diseases, excessive BAFF/APRIL signaling can sustain self-reactive B cells and the plasma cells that secrete harmful autoantibodies, contributing to tissue damage. TACI-Fc is a fusion protein built from the extracellular portion of TACI, a natural receptor for both BAFF and APRIL, joined to an antibody fragment; it works as a decoy that binds and neutralizes both cytokines before they can engage their receptors on B cells. Targeting both ligands simultaneously, rather than BAFF alone, is intended to suppress a broader range of B-cell and plasma-cell populations, since some long-lived antibody-secreting plasma cells depend more heavily on APRIL than on BAFF for survival. This dual blockade is being explored across autoimmune and inflammatory conditions in which B-cell-driven autoantibody production plays a central role, including lupus and certain kidney and rheumatologic diseases. Because B cells and plasma cells are also essential for normal immune defense, modulating this pathway carries an inherent balance between reducing autoimmune activity and preserving protective antibody responses.