Tumor necrosis factor ligand superfamily member 13B (soluble form), B cell activating factor, B lymphocyte stimulator, BLyS, Dendritic cell-derived TNF-like molecule, TNF- and APOL-related leukocyte expressed ligand 1, TALL-1, CD257, TNFSF20, ZTNF4
B cell activating factor (BAFF) belongs to the tumor necrosis factor (TNF) superfamily of cytokines produced by various immune cells, such as dendritic cells, monocytes and B cells. Structurally, BAFF represents a type II transmembrane protein, which is cleaved into a soluble form. As homotrimer, BAFF interacts with its receptors expressed on B cells, including BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA). Noteworthy, BAFF can also assemble with APRIL to form heteromers, thereby modulating receptor-binding specificities and activities. BAFF plays a pivotal role in regulating B cell development at multiple stages, from early B cell development in the bone marrow to peripheral B cell maturation and maintenance. Moreover, BAFF signaling is essential for maintaining the survival of peripheral B cells in secondary lymphoid organs. BAFF influences the magnitude and quality of antibody responses by regulating B-cell activation and differentiation. In response to antigenic stimulation, BAFF induces the generation of antibody-secreting plasma cells and the production of antibodies. Furthermore, BAFF promotes class switching and the affinity maturation process, contributing to the diversification and optimization of antibody responses. Elevated expression levels of BAFF and excessive BAFF signaling lead to aberrant B cell activation, production of autoantibodies, and tissue damage, resulting in the development and progression of B cell malignancies as well as autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis. Therefore, several BAFF-targeted therapies have been developed that aim to modulate B cell homeostasis, suppress autoantibody production and alleviate autoimmune symptoms.
