BAFF / BLyS (B-lymphocyte stimulator)

Class

Monoclonal antibody (human IgG1λ)

Pathway

B-cell survival/maturation signaling

BAFF (B-cell activating factor, also known as BLyS) is a cytokine that signals to developing B lymphocytes and provides the survival cues these cells need to mature and avoid programmed cell death. It binds three receptors on B cells, most notably BAFF-R, and this signaling axis determines how many B cells persist beyond early developmental checkpoints. In autoimmune diseases, particularly systemic lupus erythematosus, elevated BAFF levels are thought to allow self-reactive B cells that would normally be eliminated to survive and mature into antibody-producing cells, contributing to the production of autoantibodies and immune complex-mediated tissue damage. Neutralizing BAFF with a monoclonal antibody removes this survival signal, leading to a reduction in circulating B cells, especially in the naive and transitional subsets that depend most heavily on BAFF for survival. This approach targets a fundamental checkpoint in B-cell biology rather than eliminating B cells directly, offering a mechanistically distinct alternative to therapies that deplete B cells outright. The rationale extends broadly across autoimmune and inflammatory conditions in which pathogenic antibody production plays a central role, since dampening the pool of available B cells can reduce the substrate for ongoing autoreactive antibody generation.