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Gene Review

TNFSF13B  -  tumor necrosis factor (ligand) superfamily...

Homo sapiens

Synonyms: B lymphocyte stimulator, B-cell-activating factor, BAFF, BLYS, BLyS, ...
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Disease relevance of TNFSF13B


High impact information on TNFSF13B

  • APRIL is a related factor that shares receptors with BAFF yet appears to play a different biological role [6].
  • BAFF overexpression leads to an expanded B cell compartment and autoimmunity in mice, and elevated amounts of BAFF can be found in the serum of autoimmune patients [6].
  • Ligand-receptor binding revealed by the TNF family member TALL-1 [7].
  • Administration of soluble recombinant BLyS to mice disrupted splenic B and T cell zones and resulted in elevated serum immunoglobulin concentrations [8].
  • The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation [8].

Chemical compound and disease context of TNFSF13B


Biological context of TNFSF13B


Anatomical context of TNFSF13B

  • TALL-1 is a recently identified member of the tumor necrosis factor (TNF) family that costimulates B lymphocyte proliferation [1].
  • APRIL and BAFF were potent survival factors for exogenous cytokine-dependent myeloma cell lines and were autocrine growth factors for the RPMI8226 and L363 autonomously growing cell lines [3].
  • NLCs expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells [4].
  • Finally, we provide evidence that BLyS is expressed by MM cells and is present in the bone marrow of patients with MM [17].
  • In summary, our results suggest that macrophage- and DC-derived B-cell-activating factor belonging to the TNF family (BAFF) represents a key molecule by which macrophages and DCs directly regulate human B-cell proliferative responses to T-cell-independent stimuli [18].

Associations of TNFSF13B with chemical compounds

  • BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone [3].
  • Second, shotgun alanine scanning of BCMA was used to map critical residues for either APRIL or BAFF binding [19].
  • Supernatants of cultures with BAFF and APRIL contained elevated PGE2 [20].
  • Of relevance to both protective and pathogenic responses to Ag is the recent finding that soluble molecules of the innate immune system, i.e., IL-4, B cell-activation factor of the TNF family (BAFF), and C3, exhibit significant synergy in promoting the clonal expansion of human B2 cells following low-level BCR ligation [20].
  • B lymphocyte stimulator (BLyS) is a member of tumor necrosis factor (TNF) family [21].
  • This translated into a survival advantage of 16 days (P < 0.05), a decrease in tartrate-resistant acid phosphatase-positive osteoclasts, and a reduction in radiologically evident lytic lesions in anti-BAFF-treated animals [22].
  • These findings indicate that as neutrophils enter the site of inflammation, they release surface-expressed BLyS in a TNFalpha-dependent manner, and thus may contribute to local stimulation of autoimmune B cell responses [23].

Physical interactions of TNFSF13B


Regulatory relationships of TNFSF13B


Other interactions of TNFSF13B

  • Overexpression of BCMA activates NF-kappaB, and this activation is potentiated by TALL-1 [1].
  • Altogether, these data suggest that APRIL/BAFF inhibitors may be of clinical value in MM [3].
  • Outside of the turn, mutagenesis identifies additional hydrophobic contacts that enhance the BAFF-BR3 interaction [10].
  • TACI expression is a good indicator of a BAFF-binding receptor [15].
  • Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas [2].

Analytical, diagnostic and therapeutic context of TNFSF13B


  1. B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1. Shu, H.B., Johnson, H. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas. Fu, L., Lin-Lee, Y.C., Pham, L.V., Tamayo, A., Yoshimura, L., Ford, R.J. Blood (2006) [Pubmed]
  3. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Moreaux, J., Legouffe, E., Jourdan, E., Quittet, P., Rème, T., Lugagne, C., Moine, P., Rossi, J.F., Klein, B., Tarte, K. Blood (2004) [Pubmed]
  4. Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha. Nishio, M., Endo, T., Tsukada, N., Ohata, J., Kitada, S., Reed, J.C., Zvaifler, N.J., Kipps, T.J. Blood (2005) [Pubmed]
  5. B lymphocyte stimulator expression in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis patients. Hong, S.D., Reiff, A., Yang, H.T., Migone, T.S., Ward, C.D., Marzan, K., Shaham, B., Phei, W.C., Garza, J., Bernstein, B., Stohl, W. Arthritis Rheum. (2009) [Pubmed]
  6. BAFF AND APRIL: a tutorial on B cell survival. Mackay, F., Schneider, P., Rennert, P., Browning, J. Annu. Rev. Immunol. (2003) [Pubmed]
  7. Ligand-receptor binding revealed by the TNF family member TALL-1. Liu, Y., Hong, X., Kappler, J., Jiang, L., Zhang, R., Xu, L., Pan, C.H., Martin, W.E., Murphy, R.C., Shu, H.B., Dai, S., Zhang, G. Nature (2003) [Pubmed]
  8. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Moore, P.A., Belvedere, O., Orr, A., Pieri, K., LaFleur, D.W., Feng, P., Soppet, D., Charters, M., Gentz, R., Parmelee, D., Li, Y., Galperina, O., Giri, J., Roschke, V., Nardelli, B., Carrell, J., Sosnovtseva, S., Greenfield, W., Ruben, S.M., Olsen, H.S., Fikes, J., Hilbert, D.M. Science (1999) [Pubmed]
  9. Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes. Karpusas, M., Cachero, T.G., Qian, F., Boriack-Sjodin, A., Mullen, C., Strauch, K., Hsu, Y.M., Kalled, S.L. J. Mol. Biol. (2002) [Pubmed]
  10. BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site. Gordon, N.C., Pan, B., Hymowitz, S.G., Yin, J., Kelley, R.F., Cochran, A.G., Yan, M., Dixit, V.M., Fairbrother, W.J., Starovasnik, M.A. Biochemistry (2003) [Pubmed]
  11. Targeting B-lymphocyte stimulator/b-cell activating factor and a proliferation-inducing ligand in hematologic malignancies. Shivakumar, L., Ansell, S. Clinical lymphoma & myeloma. (2006) [Pubmed]
  12. Analysis of a human immunodeficiency virus type 1 isolate carrying a truncated transmembrane glycoprotein. Shimizu, H., Hasebe, F., Tsuchie, H., Morikawa, S., Ushijima, H., Kitamura, T. Virology (1992) [Pubmed]
  13. Effect of dexamethasone on the growth of human lymphoblastoid cell lines. Sasaki, R., Mishima, Y., Srivastava, B.I., Minowada, J. Jpn. J. Med. (1982) [Pubmed]
  14. B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom macroglobulinemia. Elsawa, S.F., Novak, A.J., Grote, D.M., Ziesmer, S.C., Witzig, T.E., Kyle, R.A., Dillon, S.R., Harder, B., Gross, J.A., Ansell, S.M. Blood (2006) [Pubmed]
  15. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature. Moreaux, J., Cremer, F.W., Reme, T., Raab, M., Mahtouk, K., Kaukel, P., Pantesco, V., De Vos, J., Jourdan, E., Jauch, A., Legouffe, E., Moos, M., Fiol, G., Goldschmidt, H., Rossi, J.F., Hose, D., Klein, B. Blood (2005) [Pubmed]
  16. EBV-encoded latent membrane protein 1 cooperates with BAFF/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching. He, B., Raab-Traub, N., Casali, P., Cerutti, A. J. Immunol. (2003) [Pubmed]
  17. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Novak, A.J., Darce, J.R., Arendt, B.K., Harder, B., Henderson, K., Kindsvogel, W., Gross, J.A., Greipp, P.R., Jelinek, D.F. Blood (2004) [Pubmed]
  18. Macrophage- and dendritic cell--dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF. Craxton, A., Magaletti, D., Ryan, E.J., Clark, E.A. Blood (2003) [Pubmed]
  19. Engineering an APRIL-specific B cell maturation antigen. Patel, D.R., Wallweber, H.J., Yin, J., Shriver, S.K., Marsters, S.A., Gordon, N.C., Starovasnik, M.A., Kelley, R.F. J. Biol. Chem. (2004) [Pubmed]
  20. APRIL and BAFF promote increased viability of replicating human B2 cells via mechanism involving cyclooxygenase 2. Mongini, P.K., Inman, J.K., Han, H., Fattah, R.J., Abramson, S.B., Attur, M. J. Immunol. (2006) [Pubmed]
  21. A novel BLyS antagonist peptide designed based on the 3-D complex structure of BCMA and BLyS. Sun, J., Feng, J., Li, Y., Shen, B. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  22. Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model. Neri, P., Kumar, S., Fulciniti, M.T., Vallet, S., Chhetri, S., Mukherjee, S., Tai, Y., Chauhan, D., Tassone, P., Venuta, S., Munshi, N.C., Hideshima, T., Anderson, K.C., Raje, N. Clin. Cancer Res. (2007) [Pubmed]
  23. Tumor necrosis factor alpha activates release of B lymphocyte stimulator by neutrophils infiltrating the rheumatoid joint. Assi, L.K., Wong, S.H., Ludwig, A., Raza, K., Gordon, C., Salmon, M., Lord, J.M., Scheel-Toellner, D. Arthritis Rheum. (2007) [Pubmed]
  24. Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS. Wu, Y., Bressette, D., Carrell, J.A., Kaufman, T., Feng, P., Taylor, K., Gan, Y., Cho, Y.H., Garcia, A.D., Gollatz, E., Dimke, D., LaFleur, D., Migone, T.S., Nardelli, B., Wei, P., Ruben, S.M., Ullrich, S.J., Olsen, H.S., Kanakaraj, P., Moore, P.A., Baker, K.P. J. Biol. Chem. (2000) [Pubmed]
  25. TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation. Xia, X.Z., Treanor, J., Senaldi, G., Khare, S.D., Boone, T., Kelley, M., Theill, L.E., Colombero, A., Solovyev, I., Lee, F., McCabe, S., Elliott, R., Miner, K., Hawkins, N., Guo, J., Stolina, M., Yu, G., Wang, J., Delaney, J., Meng, S.Y., Boyle, W.J., Hsu, H. J. Exp. Med. (2000) [Pubmed]
  26. The growth factor fusion construct containing B-lymphocyte stimulator (BLyS) and the toxin rGel induces apoptosis specifically in BAFF-R-positive CLL cells. Nimmanapalli, R., Lyu, M.A., Du, M., Keating, M.J., Rosenblum, M.G., Gandhi, V. Blood (2007) [Pubmed]
  27. Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. He, B., Chadburn, A., Jou, E., Schattner, E.J., Knowles, D.M., Cerutti, A. J. Immunol. (2004) [Pubmed]
  28. TNFR-associated factor-3 is associated with BAFF-R and negatively regulates BAFF-R-mediated NF-kappa B activation and IL-10 production. Xu, L.G., Shu, H.B. J. Immunol. (2002) [Pubmed]
  29. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt's lymphoma. Ogden, C.A., Pound, J.D., Batth, B.K., Owens, S., Johannessen, I., Wood, K., Gregory, C.D. J. Immunol. (2005) [Pubmed]
  30. BAFF synthesis by rheumatoid synoviocytes is positively controlled by alpha5beta1 integrin stimulation and is negatively regulated by tumor necrosis factor alpha and Toll-like receptor ligands. Alsaleh, G., Messer, L., Semaan, N., Boulanger, N., Gottenberg, J.E., Sibilia, J., Wachsmann, D. Arthritis Rheum. (2007) [Pubmed]
  31. Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Kern, C., Cornuel, J.F., Billard, C., Tang, R., Rouillard, D., Stenou, V., Defrance, T., Ajchenbaum-Cymbalista, F., Simonin, P.Y., Feldblum, S., Kolb, J.P. Blood (2004) [Pubmed]
  32. Rapid expression cloning of receptors using epitope-tagged ligands and high-speed cell sorting. Robeva, A.S., Yan-Neale, Y., Burfeind, P., Bodian, D.L., Chirn, G.W., Kolbinger, F., Labow, M., Vallon, R.D. Cytometry. Part A : the journal of the International Society for Analytical Cytology. (2003) [Pubmed]
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