baff

BAFF, or B-cell activating factor, is a cytokine of the tumor necrosis factor (TNF) ligand superfamily that regulates B cell maturation, survival, and immune function. In humans, BAFF is encoded by the TNFSF13B gene. It is produced by a variety of cells of the myeloid lineage, including dendritic cells, monocytes, macrophages, and neutrophils, and can be expressed as a membrane-bound protein or released as a soluble ligand through proteolytic processing.

BAFF exerts its effects by binding to three receptors on B cells: BAFF-R (TNFRSF13C), TACI (TNFRSF13B), and BCMA (TNFRSF17). BAFF binds BAFF-R with high affinity and TACI/BCMA with lower affinity; APRIL, a related TNF family member, binds TACI and BCMA but not BAFF-R. Through these receptors, BAFF promotes survival of transitional and mature B cells, supports class-switch recombination, and contributes to germinal center formation and B cell homeostasis. Deficiency of BAFF leads to reduced mature B cell numbers, whereas overexpression can drive B cell–mediated autoimmunity.

Clinically, dysregulated BAFF signaling is implicated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, and in certain B cell malignancies. Therapeutically, belimumab, a human monoclonal antibody against BAFF, is approved for SLE, and other BAFF inhibitors have been investigated in clinical trials.