BAFF (BLyS)

Class

Monoclonal antibody (Belimumab, IV formulation)

Pathway

B-cell survival/BAFF signaling

BAFF (B-cell activating factor, also known as BLyS, B-lymphocyte stimulator) is a cytokine that promotes the survival and maturation of B cells, the white blood cells responsible for producing antibodies. B cells require survival signals from BAFF, delivered through receptors on their surface, to persist beyond an early developmental checkpoint; without adequate BAFF signaling, self-reactive B cells that would otherwise be eliminated may instead survive and mature into antibody-producing cells. In autoimmune diseases such as lupus, elevated BAFF levels are thought to support the persistence of these self-reactive B-cell populations, contributing to the production of autoantibodies that drive tissue damage. Neutralizing circulating BAFF with a monoclonal antibody reduces the survival signal available to B cells, favoring attrition of these cells, particularly among the less mature, more autoreactive subsets. This approach differs from directly eliminating B cells outright: it does not remove the entire B-cell compartment but shifts the balance toward reduced survival of newly generated B cells, offering a rationale for use in systemic autoimmune conditions where broad B-cell depletion carries higher infection risk. The mechanism is broadly relevant across antibody-mediated autoimmune diseases where excess B-cell survival contributes to pathology.