BLYS

BLyS, also known as B-lymphocyte stimulator or BAFF (B cell activating factor), is a cytokine in the tumor necrosis factor (TNF) superfamily. In humans it is encoded by the TNFSF13B gene and plays a key role in B cell biology.

BLyS is produced by cells of the myeloid lineage, including monocytes and dendritic cells, as well as by neutrophils and certain stromal cells. It exists in soluble forms and, in some contexts, as a membrane-bound form. BLyS signals through three receptors on B cells: BAFF-R (BR3), TACI (TNFRSF13B), and BCMA (TNFRSF17). APRIL, another TNF family member, can bind to TACI and BCMA with overlapping functions.

Biological function of BLyS includes promoting survival and maturation of B cells, particularly from transitional to mature stages, and supporting germinal center responses and isotype switching. BAFF-R is the main receptor mediating mature B cell survival; APRIL primarily engages TACI and BCMA. Proper BLyS signaling is essential for peripheral B cell homeostasis, while dysregulation can contribute to autoimmunity.

Clinical relevance of BLyS centers on its association with autoimmune diseases. Elevated BLyS levels have been observed in systemic lupus erythematosus (SLE) and other autoimmune conditions, correlating with disease activity in some cases. In animal models, excess BLyS promotes B cell–driven autoimmunity, whereas BLyS deficiency reduces B cell numbers.

Therapeutically, BLyS inhibitors have been developed. Belimumab is a human monoclonal antibody against soluble BLyS and is approved for SLE. Other agents, such as tabalumab (anti-BAFF) and atacicept (a TACI-Ig fusion that inhibits BLyS and APRIL), have had mixed results or discontinuations in development.