TNFSF13B

TNFSF13B is the gene that encodes BAFF, a member of the tumor necrosis factor (TNF) ligand superfamily. BAFF, also called BLYS (B cell activating factor), functions as a cytokine that promotes B cell survival, maturation, and antibody production. The protein is a type II transmembrane protein that can be proteolytically cleaved to release a soluble ligand. BAFF is produced by cells of the myeloid lineage, including dendritic cells and macrophages, as well as by stromal cells in lymphoid tissues, and its expression can be upregulated during immune activation.

BAFF exerts its effects by binding to three receptors on B cells: BAFF-R (TNFRSF13C), TACI (TNFRSF13B), and BCMA (TNFRSF17). It forms homotrimers and can assemble into higher-order structures, enabling potent signaling that supports B cell lineage survival and maturation, particularly transitional and marginal zone B cells, and enhances immunoglobulin production. Regulation of BAFF levels is critical for B cell tolerance; excessive BAFF can permit the survival of autoreactive B cells and has been implicated in autoimmunity.

Clinical relevance of BAFF includes its association with autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, where elevated BAFF activity is observed in some patients. Therapeutic strategies targeting BAFF aim to reduce pathogenic B cell activity; belimumab, an antibody against soluble BAFF, is approved for the treatment of SLE, reflecting the clinical importance of BAFF in humoral immunity. Variants in TNFSF13B have been studied for potential associations with autoimmune disease risk and immunoglobulin regulation.