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; 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. [cite journal | author = Oren,D.A., Li,Y., Volovik,Y., Morris,T.S., Dharia,C., Das,K., Galperina,O., Gentz,R. and Arnold,E. | title = Structural basis of BLyS receptor recognition | journal = Nat. Struct. Biol. | year = 2002 | volume = 9 |pages = 288–292 | pmid=11862220 | doi = 10.1038/nsb769]

References

Further reading

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citations =
*cite journal | author=Nardelli B, Moore PA, Li Y, Hilbert DM |title=B lymphocyte stimulator (BLyS): a therapeutic trichotomy for the treatment of B lymphocyte diseases. |journal=Leuk. Lymphoma |volume=43 |issue= 7 |pages= 1367–73 |year= 2003 |pmid= 12389615 |doi=
*cite journal | author=Zhou T, Zhang J, Carter R, Kimberly R |title=BLyS and B cell autoimmunity. |journal=Curr. Dir. Autoimmun. |volume=6 |issue= |pages= 21–37 |year= 2003 |pmid= 12408045 |doi=
*cite journal | author=Stohl W |title=A therapeutic role for BLyS antagonists. |journal=Lupus |volume=13 |issue= 5 |pages= 317–22 |year= 2005 |pmid= 15230285 |doi=
*cite journal | author=Quartuccio L, Fabris M, Ferraccioli G |title= [B lymphocyte stimulator (BLyS) and monocytes: possible role in autoimmune diseases with a particular reference to rheumatoid arthritis] |journal=Reumatismo |volume=56 |issue= 3 |pages= 143–6 |year= 2004 |pmid= 15470519 |doi=
*cite journal | author=Sutherland AP, Mackay F, Mackay CR |title=Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas. |journal=Pharmacol. Ther. |volume=112 |issue= 3 |pages= 774–86 |year= 2007 |pmid= 16863659 |doi= 10.1016/j.pharmthera.2006.06.002
*cite journal | author=Bossen C, Schneider P |title=BAFF, APRIL and their receptors: structure, function and signaling. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 263–75 |year= 2007 |pmid= 16914324 |doi= 10.1016/j.smim.2006.04.006
*cite journal | author=Brink R |title=Regulation of B cell self-tolerance by BAFF. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 276–83 |year= 2007 |pmid= 16916609 |doi= 10.1016/j.smim.2006.04.003
*cite journal | author=Tangye SG, Bryant VL, Cuss AK, Good KL |title=BAFF, APRIL and human B cell disorders. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 305–17 |year= 2007 |pmid= 16916610 |doi= 10.1016/j.smim.2006.04.004
*cite journal | author=Treml LS, Crowley JE, Cancro MP |title=BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 297–304 |year= 2007 |pmid= 16919470 |doi= 10.1016/j.smim.2006.07.001
*cite journal | author=Woodland RT, Schmidt MR, Thompson CB |title=BLyS and B cell homeostasis. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 318–26 |year= 2007 |pmid= 16931037 |doi= 10.1016/j.smim.2006.06.001
*cite journal | author=Kalled SL |title=Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 290–6 |year= 2007 |pmid= 16931038 |doi= 10.1016/j.smim.2006.06.002
*cite journal | author=Mackay F, Leung H |title=The role of the BAFF/APRIL system on T cell function. |journal=Semin. Immunol. |volume=18 |issue= 5 |pages= 284–9 |year= 2007 |pmid= 16931039 |doi= 10.1016/j.smim.2006.04.005
*cite journal | author=Bosello S, Pers JO, Rochas C, "et al." |title=BAFF and rheumatic autoimmune disorders: implications for disease management and therapy. |journal=International journal of immunopathology and pharmacology |volume=20 |issue= 1 |pages= 1–8 |year= 2007 |pmid= 17346422 |doi=
*cite journal | author=Shu HB, Hu WH, Johnson H |title=TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. |journal=J. Leukoc. Biol. |volume=65 |issue= 5 |pages= 680–3 |year= 1999 |pmid= 10331498 |doi=
*cite journal | author=Mukhopadhyay A, Ni J, Zhai Y, "et al." |title=Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear factor-kappaB, and c-Jun NH2-terminal kinase. |journal=J. Biol. Chem. |volume=274 |issue= 23 |pages= 15978–81 |year= 1999 |pmid= 10347144 |doi=
*cite journal | author=Schneider P, MacKay F, Steiner V, "et al." |title=BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. |journal=J. Exp. Med. |volume=189 |issue= 11 |pages= 1747–56 |year= 1999 |pmid= 10359578 |doi=
*cite journal | author=Moore PA, Belvedere O, Orr A, "et al." |title=BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. |journal=Science |volume=285 |issue= 5425 |pages= 260–3 |year= 1999 |pmid= 10398604 |doi=
*cite journal | author=Tribouley C, Wallroth M, Chan V, "et al." |title=Characterization of a new member of the TNF family expressed on antigen presenting cells. |journal=Biol. Chem. |volume=380 |issue= 12 |pages= 1443–7 |year= 2000 |pmid= 10661873 |doi=
*cite journal | author=Gross JA, Johnston J, Mudri S, "et al." |title=TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. |journal=Nature |volume=404 |issue= 6781 |pages= 995–9 |year= 2000 |pmid= 10801128 |doi= 10.1038/35010115
*cite journal | author=Shu HB, Johnson H |title=B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 16 |pages= 9156–61 |year= 2000 |pmid= 10908663 |doi= 10.1073/pnas.160213497

External links

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