B-cell activating factor (BAFF), also known as Blys, TALL-1, TNAK, and zTNF4, is a TNF ligand superfamily member and has been designated TNFSF13B. Produced by macrophages, dendritic cells, and T lymphocytes, BAFF promotes the survival of B cells and is essential for B cell maturation. BAFF binds to three TNF receptor superfamily members: B-cell maturation antigen (BCMA/TNFRSF17), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI/TNFRSF13B) and BAFF receptor (BAFF R/BR3/TNFRSF 13C). These receptors are type III transmembrane proteins that lack a signal peptide. Whereas TACI and BCMA bind BAFF and another TNF superfamily ligand, APRIL (a proliferation-inducing ligand), BAFF R selectively binds BAFF. The BAFF R extracellular domain lacks the TNF receptor canonical cysteine-rich domain (CRD) and contains only a partial CRD with four cysteine residues. Human and mouse BAFF R share 56 % a.a. sequence identity. BAFF R is highly expressed in spleen, lymph node and resting B cells. It is also expressed at lower levels in activated B cell, in resting CD4+ T cells, in thymus and peripheral blood leukocytes.
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