B-cell activating factor

B-cell activating factor (BAFF) is the Tumor necrosis factor ligand superfamily member 13B (TNFLSF13B), also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule (CD257 antigen). BAFF is a 285-amino acid long peptide glycoprotein which undergoes glycosylation at site #124. It is expressed as transmembrane protein on different cells, such as monocytes, dendritic cells and bone marrow stromal cells. The transmembrane form can be cleaved from the membrane, generating a soluble protein fragment. BAFF is the natural ligand of three unusual Tumor Necrosis Family Receptors named BAFF-R, TACI, and BCMA, all of which have differing binding affinities for it. These receptors are expressed mainly on mature B lymphocytes (TACI is also found on a subset of T-cells and BCMA on plasma cells). TACI binds worst since its affinity is higher for a protein similar to BAFF, called A Proliferation Inducing Ligand (APRIL). BCMA displays an intermediate binding phenotype and will work with either BAFF or APRIL to varying degrees. Signaling trough BAFF-R and BCMA stimulates B lymphocytes to undergo proliferation and to counter apoptosis. All these ligands act as heterotrimers (i.e. three of the same molecule) interacting with heterotrimeric receptors.