B-cell activating factor (BAFF), also known as BLyS, TALL-1, THANK, and TNFSF13B, is a 32 kDa transmembrane glycoprotein in the TNF ligand superfamily. It is involved in multiple aspects of immune system regulation, particularly towards B cells . Mature mouse BAFF consists of a 47 amino acid (aa) cytoplasmic domain, a 21 aa transmembrane segment, and a 241 aa extracellular domain (ECD) with a stalk region and one TNF-like domain . Within aa 127-309 of the ECD, mouse BAFF shares 72% aa sequence identity with human BAFF. It can be expressed as a homotrimer or as a heteromer in association with the related TNFSF member APRIL . A 18 kDa fragment containing the TNF-like domain can be released by proteolysis between Arg126 and Ala127. Soluble BAFF is stored intracellularly in neutrophils and released upon inflammatory stimulation . deltaBAFF can form heteromers with BAFF and negatively regulates BAFF function . BAFF is produced by many hematopoietic cell types including by monocytes, macrophages, neutrophils, dendritic cells, and T cells and also by adipocytes. Both BAFF and APRIL are functional ligands for the TNF receptor superfamily members BCMA and TACI, and BAFF additionally binds and signals through BAFF R. All three receptors are primarily expressed by B cells . BAFF plays a critical role in the development and survival of B lineage cells . Mice that over-express BAFF exhibit elevated B cell numbers, increased formati of germinal centers, and symptoms of autoimmunity. Soluble BAFF is elevated in B cell malignancies, autoimmunity, and other immune disorders . In addition, BAFF costimulates T cell activation, promotes a Th1 biased immune response, and promotes the expansion of Treg cells . BAFF also promotes monocyte survival, proinflammatory cytokine secretion, and differentiation to macrophages .
