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Gene Review

TNFRSF13B  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: CD267, CVID, CVID2, IGAD2, RYZN, ...
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Disease relevance of TNFRSF13B


High impact information on TNFRSF13B


Chemical compound and disease context of TNFRSF13B


Biological context of TNFRSF13B


Anatomical context of TNFRSF13B

  • Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function [9].
  • Both ligands can bind the two members of the TNF receptor family, namely the transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), as well as B-cell maturation antigen (BCMA) [12].
  • BAFF-R expression increased initially and then decreased with a corresponding induction of TACI and BCMA expression during differentiation to plasma cells (PCs) [13].
  • Cross-linking of this lymphocyte-specific protein, designated TACI (transmembrane activator and CAML-interactor), on the surface of transfected Jurkat cells with TACI-specific antibodies led to activation of the transcription factors NF-AT, AP-1, and NFkappaB [14].
  • Unlike their putative germinal center B-cell precursors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacytoid B cells [15].

Associations of TNFRSF13B with chemical compounds

  • Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro [16].
  • TACI binding appears to require heparan sulfate posttranslational modifications of syndecan-2, because free heparin or pretreatment with heparitinase blocked the interaction [17].
  • The human Taci gene (Transmembrane Activator and CAML Interactor) encodes a recently discovered member of the Tumor Necrosis Factor Receptor family [18].
  • We recommend that all CVID patients with evidence of an enteropathy be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological sequelae [19].
  • The Cu(II) complex of the ligand all-cis-2,4,6-triamino-1,3,5-trihydroxycyclohexane (TACI) is a very efficient catalyst of the cleavage of plasmid DNA in the absence of any added cofactor [20].

Physical interactions of TNFRSF13B

  • Expression of TACI in HEK293T cells confers on the cells the ability to bind BLyS with subnanomolar affinity [21].
  • Syndecan-2 bound TACI but bound neither BAFF-R nor BCMA [17].

Regulatory relationships of TNFRSF13B

  • Importantly, BAFF-R and CD40 enhanced B cell responsiveness to TACI-mediated suppression [22].
  • TACI-induced activation of NF-AT was specifically blocked by a dominant-negative CAML mutant, thus implicating CAML as a signaling intermediate [14].
  • This is the first identification of ligands that selectively activate TACI without simultaneously triggering BCMA or BAFF-R [17].
  • B cells from individuals with TACI mutations did not produce IgG and IgA in response to the TACI ligand a proliferation-inducing ligand (APRIL), probably reflecting impaired isotype switching [23].
  • In support of this notion, mouse TACI was found to activate NFAT, NFkB, and AP1 transcription factors in a transient transfection assay [18].

Other interactions of TNFRSF13B

  • TACI expression is a good indicator of a BAFF-binding receptor [11].
  • BLyS and APRIL are capable of signaling through TACI to mediate NF-kappaB responses in HEK293 cells [21].
  • By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6 [16].
  • Thus, the recent discovery of deletions in the ICOS, BAFF-R and TACI genes leading to disturbances in late B cell differentiation and hypogammaglobulinaemia underline the potential impact of targeting these molecules for therapeutic strategies in autoimmune disorders [24].

Analytical, diagnostic and therapeutic context of TNFRSF13B

  • Molecular cloning and functional characterization of murine transmembrane activator and CAML interactor (TACI) with chromosomal localization in human and mouse [18].
  • The Taci gene was localized to human Chromosome (Chr) 17p11 by fluorescence in situ hybridization [18].
  • We have investigated the effects of a new omega-conotoxin, CVID (AM-336), and compared them with omega-conotoxin GVIA (SNX-124), omega-conotoxin MVIIA (SNX-111) and morphine in a spinal nerve ligation model of neuropathic pain in the rat [25].
  • In this study, a profound alteration of the T cell receptor repertoire was noted, especially in CD8(+) T cells, in CVID patients when compared to a control group [26].


  1. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Salzer, U., Chapel, H.M., Webster, A.D., Pan-Hammarström, Q., Schmitt-Graeff, A., Schlesier, M., Peter, H.H., Rockstroh, J.K., Schneider, P., Schäffer, A.A., Hammarström, L., Grimbacher, B. Nat. Genet. (2005) [Pubmed]
  2. 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]
  3. Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm: a preliminary study. Inoue, K., Mineharu, Y., Inoue, S., Yamada, S., Matsuda, F., Nozaki, K., Takenaka, K., Hashimoto, N., Koizumi, A. Circulation (2006) [Pubmed]
  4. TACI is mutant in common variable immunodeficiency and IgA deficiency. Castigli, E., Wilson, S.A., Garibyan, L., Rachid, R., Bonilla, F., Schneider, L., Geha, R.S. Nat. Genet. (2005) [Pubmed]
  5. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Seshasayee, D., Valdez, P., Yan, M., Dixit, V.M., Tumas, D., Grewal, I.S. Immunity (2003) [Pubmed]
  6. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Pan-Hammarström, Q., Salzer, U., Du, L., Björkander, J., Cunningham-Rundles, C., Nelson, D.L., Bacchelli, C., Gaspar, H.B., Offer, S., Behrens, T.W., Grimbacher, B., Hammarström, L. Nat. Genet. (2007) [Pubmed]
  7. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Castigli, E., Wilson, S., Garibyan, L., Rachid, R., Bonilla, F., Schneider, L., Morra, M., Curran, J., Geha, R. Nat. Genet. (2007) [Pubmed]
  8. Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia-telangiectasia. Sanal, O., Ersoy, F., Yel, L., Tezcan, I., Metin, A., Ozyürek, H., Gariboglu, S., Fikrig, S., Berkel, A.I., Rijkers, G.T., Zegers, B.J. J. Clin. Immunol. (1999) [Pubmed]
  9. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Yu, G., Boone, T., Delaney, J., Hawkins, N., Kelley, M., Ramakrishnan, M., McCabe, S., Qiu, W.R., Kornuc, M., Xia, X.Z., Guo, J., Stolina, M., Boyle, W.J., Sarosi, I., Hsu, H., Senaldi, G., Theill, L.E. Nat. Immunol. (2000) [Pubmed]
  10. Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding. Hymowitz, S.G., Patel, D.R., Wallweber, H.J., Runyon, S., Yan, M., Yin, J., Shriver, S.K., Gordon, N.C., Pan, B., Skelton, N.J., Kelley, R.F., Starovasnik, M.A. J. Biol. Chem. (2005) [Pubmed]
  11. 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]
  12. The uncertain glory of APRIL. Medema, J.P., Planelles-Carazo, L., Hardenberg, G., Hahne, M. Cell Death Differ. (2003) [Pubmed]
  13. BAFF supports human B cell differentiation in the lymphoid follicles through distinct receptors. Zhang, X., Park, C.S., Yoon, S.O., Li, L., Hsu, Y.M., Ambrose, C., Choi, Y.S. Int. Immunol. (2005) [Pubmed]
  14. NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily. von Bülow, G.U., Bram, R.J. Science (1997) [Pubmed]
  15. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Chiu, A., Xu, W., He, B., Dillon, S.R., Gross, J.A., Sievers, E., Qiao, X., Santini, P., Hyjek, E., Lee, J.W., Cesarman, E., Chadburn, A., Knowles, D.M., Cerutti, A. Blood (2007) [Pubmed]
  16. 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]
  17. Selective activation of TACI by syndecan-2. Bischof, D., Elsawa, S.F., Mantchev, G., Yoon, J., Michels, G.E., Nilson, A., Sutor, S.L., Platt, J.L., Ansell, S.M., von Bulow, G., Bram, R.J. Blood (2006) [Pubmed]
  18. Molecular cloning and functional characterization of murine transmembrane activator and CAML interactor (TACI) with chromosomal localization in human and mouse. von Bülow, G.U., Russell, H., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Bram, R.J. Mamm. Genome (2000) [Pubmed]
  19. Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Aslam, A., Misbah, S.A., Talbot, K., Chapel, H. Clin. Immunol. (2004) [Pubmed]
  20. Efficient plasmid DNA cleavage by a mononuclear copper(II) complex. Sissi, C., Mancin, F., Gatos, M., Palumbo, M., Tecilla, P., Tonellato, U. Inorganic chemistry. (2005) [Pubmed]
  21. 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]
  22. TACI attenuates antibody production costimulated by BAFF-R and CD40. Sakurai, D., Kanno, Y., Hase, H., Kojima, H., Okumura, K., Kobata, T. Eur. J. Immunol. (2007) [Pubmed]
  23. Molecular basis of common variable immunodeficiency. Castigli, E., Geha, R.S. J. Allergy Clin. Immunol. (2006) [Pubmed]
  24. Molecules involved in T-B co-stimulation and B cell homeostasis: possible targets for an immunological intervention in autoimmunity. Peter, H.H., Warnatz, K. Expert opinion on biological therapy. (2005) [Pubmed]
  25. Actions of intrathecal omega-conotoxins CVID, GVIA, MVIIA, and morphine in acute and neuropathic pain in the rat. Scott, D.A., Wright, C.E., Angus, J.A. Eur. J. Pharmacol. (2002) [Pubmed]
  26. Characterization of the T cell receptor repertoire in patients with common variable immunodeficiency: oligoclonal expansion of CD8(+) T cells. Serrano, D., Becker, K., Cunningham-Rundles, C., Mayer, L. Clin. Immunol. (2000) [Pubmed]
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