BLySBAFF

BLySBAFF, also known as BAFF or B-lymphocyte stimulator, is a cytokine of the tumor necrosis factor (TNF) ligand superfamily. In humans it is encoded by the TNFSF13B gene. BLyS/BAFF exists in soluble and membrane-associated forms and functions as a trimetric ligand that can form higher-order oligomers, engaging B cell receptors to regulate B cell fate.

BLyS/BAFF exerts its effects by binding to three receptors on B cells: BAFF-R (also called BR3, TNFRSF13C), TACI (TNFRSF13B), and BCMA (TNFRSF17). Binding to BAFF-R mainly promotes survival and maturation of mature B cells, while interaction with TACI and BCMA is implicated in class-switch recombination, antibody production, and plasma cell maintenance. The different receptor engagements help shape B cell development, homeostasis, and humoral responses across health and disease.

Dysregulation of BLyS/BAFF is linked to autoimmune and inflammatory conditions. Elevated levels or activity of BAFF is observed in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjögren’s syndrome, and correlates with disease activity in several B cell–driven disorders. Therapeutically, blockade of BAFF can reduce disease activity in SLE; belimumab, a anti-BAFF monoclonal antibody, is approved for SLE treatment. Other approaches, such as TACI-Ig fusion proteins, have been explored but with mixed clinical outcomes.

Overall, BLyS/BAFF is a key regulator of B cell survival and humoral immunity, with significant implications for autoimmune disease biology and therapy.