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; cluster of differentiation 257).
BAFF is a 285-amino acid long peptide glycoprotein which undergoes glycosylation at residue 124. It is expressed as transmembrane protein on various cell types including 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 factor 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.[1]
Nardelli B, Moore PA, Li Y, Hilbert DM (2003). "B lymphocyte stimulator (BLyS): a therapeutic trichotomy for the treatment of B lymphocyte diseases.". Leuk. Lymphoma43 (7): 1367–73. PMID 12389615.
Zhou T, Zhang J, Carter R, Kimberly R (2003). "BLyS and B cell autoimmunity.". Curr. Dir. Autoimmun.6: 21–37. PMID 12408045.
Stohl W (2005). "A therapeutic role for BLyS antagonists.". Lupus13 (5): 317–22. PMID 15230285.
Quartuccio L, Fabris M, Ferraccioli G (2004). "[B lymphocyte stimulator (BLyS) and monocytes: possible role in autoimmune diseases with a particular reference to rheumatoid arthritis]". Reumatismo56 (3): 143–6. PMID 15470519.
Bossen C, Schneider P (2007). "BAFF, APRIL and their receptors: structure, function and signaling.". Semin. Immunol.18 (5): 263–75. doi:10.1016/j.smim.2006.04.006. PMID 16914324.
Kalled SL (2007). "Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production.". Semin. Immunol.18 (5): 290–6. doi:10.1016/j.smim.2006.06.002. PMID 16931038.
Bosello S, Pers JO, Rochas C, et al. (2007). "BAFF and rheumatic autoimmune disorders: implications for disease management and therapy.". International journal of immunopathology and pharmacology20 (1): 1–8. PMID 17346422.
Shu HB, Hu WH, Johnson H (1999). "TALL-1 is a novel member of the TNF family that is down-regulated by mitogens.". J. Leukoc. Biol.65 (5): 680–3. PMID 10331498.
Mukhopadhyay A, Ni J, Zhai Y, et al. (1999). "Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear factor-kappaB, and c-Jun NH2-terminal kinase.". J. Biol. Chem.274 (23): 15978–81. PMID 10347144.
Schneider P, MacKay F, Steiner V, et al. (1999). "BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.". J. Exp. Med.189 (11): 1747–56. PMID 10359578.
Moore PA, Belvedere O, Orr A, et al. (1999). "BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator.". Science285 (5425): 260–3. PMID 10398604.
Tribouley C, Wallroth M, Chan V, et al. (2000). "Characterization of a new member of the TNF family expressed on antigen presenting cells.". Biol. Chem.380 (12): 1443–7. PMID 10661873.
Gross JA, Johnston J, Mudri S, et al. (2000). "TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease.". Nature404 (6781): 995–9. doi:10.1038/35010115. PMID 10801128.
Shu HB, Johnson H (2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1.". Proc. Natl. Acad. Sci. U.S.A.97 (16): 9156–61. doi:10.1073/pnas.160213497. PMID 10908663.