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Gene Review

Tnfsf13  -  tumor necrosis factor (ligand) superfamily...

Mus musculus

Synonyms: 2310026N09Rik, A proliferation-inducing ligand, APRIL, April, TALL2, ...
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Disease relevance of Tnfsf13

  • When overexpressed in mice, APRIL induces B-cell neoplasia, reminiscent of human B-cell chronic lymphoid leukemia (B-CLL) [1].
  • Hence, APRIL produced by inflammatory cells infiltrating lymphoma lesions may increase tumor aggressiveness and affect disease outcome [1].
  • During late April through June 2005, an outbreak of H5N1 virus infection occurred among wild birds at Qinghai Lake in China. Here, we describe the features of this outbreak [2].
  • 5) The effect of estrogen on uterine ballooning and weight gain, seen in all vehicle-injected control mice at proestrus, did not occur in 97% of the mice treated with TRDL [3].
  • Urine from grouped females delayed puberty for the months of September to April, but not for the period May through August [4].

High impact information on Tnfsf13

  • In these mice, DCs were accumulated in the thymus and spleen and produced high levels of BAFF/BLyS and APRIL, resulting in the aberrant expansion of B cells and autoreactive antibody production [5].
  • Dendritic cell-derived TNF-family ligands APRIL and/or BAFF enhance plasmablast survival and differentiation to plasma cells [6].
  • BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA [7].
  • Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness [1].
  • APRIL secreted by neutrophils accumulated on tumor cells via proteoglycan binding [1].

Biological context of Tnfsf13

  • In cultures, both recombinant BAFF and APRIL significantly promote the survival of precursor B cells whereas only BAFF can suppress apoptosis of immature B cells [8].
  • While, physiological roles for APRIL are not fully understood, BAFF is critical for B cell homeostasis and also acts as a co-stimulator of T cells [9].
  • APRIL up-regulation was only observed in high-grade B-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) [1].
  • Taken together, these results indicate disruption of the normal mouse estrous cycle by the TRDL peptide and represent the first demonstration of in vivo effects of gonadotropin-related synthetic peptides on reproductive processes [3].
  • 1) A single i.p. injection of 200 microg/g BW TRDL induced persistent vaginal estrus, characterized by the complete absence of epithelial casts in 87% of the mice treated, as determined by vaginal cytology [3].

Anatomical context of Tnfsf13


Associations of Tnfsf13 with chemical compounds

  • APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily [10].
  • A PRoliferation-Inducing TNF Ligand (APRIL) costimulates B-cell activation [1].
  • 4) Serum estradiol levels at proestrus in TRDL-treated mice were significantly lower than those in vehicle-injected control mice [3].
  • When given as five consecutive daily ip injections of 200 ug/g BW to 28-day-old prepubertal male mice, TRDL significantly increased testis weight, when compared with vehicle-injected control mice of the same age and BW (171.3 +/- 3.8 mg vs. 151.6 +/- 4.3 mg, P = 0.001) and induced a 6.5-fold increase in serum testosterone levels [13].
  • Through in vitro analyses of PB/plasma cell (PC) survival/differentiation, we show that APRIL induces the expression of Bcl-X(L) by a preferential binding to heparan sulfate proteoglycans at the surface of CD138(+) cells [14].

Regulatory relationships of Tnfsf13

  • A transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI)-Ig fusion protein (which neutralizes both BAFF and a proliferation-inducing ligand (APRIL), another TNF family member) inhibited Hg-induced autoantibody or serum IgE production [15].

Other interactions of Tnfsf13


  1. Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness. Schwaller, J., Schneider, P., Mhawech-Fauceglia, P., McKee, T., Myit, S., Matthes, T., Tschopp, J., Donze, O., Le Gal, F.A., Huard, B. Blood (2007) [Pubmed]
  2. Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. Chen, H., Li, Y., Li, Z., Shi, J., Shinya, K., Deng, G., Qi, Q., Tian, G., Fan, S., Zhao, H., Sun, Y., Kawaoka, Y. J. Virol. (2006) [Pubmed]
  3. In vivo effects of follicle-stimulating hormone-related synthetic peptides on the mouse estrous cycle. Grasso, P., Reichert, L.E. Endocrinology (1996) [Pubmed]
  4. Seasonal variation in acceleration and delay of sexual maturation in female mice by urinary chemosignals. Drickamer, L.C. J. Reprod. Fertil. (1984) [Pubmed]
  5. Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Hanada, T., Yoshida, H., Kato, S., Tanaka, K., Masutani, K., Tsukada, J., Nomura, Y., Mimata, H., Kubo, M., Yoshimura, A. Immunity (2003) [Pubmed]
  6. Dendritic cells, BAFF, and APRIL: innate players in adaptive antibody responses. MacLennan, I., Vinuesa, C. Immunity (2002) [Pubmed]
  7. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Gross, J.A., Dillon, S.R., Mudri, S., Johnston, J., Littau, A., Roque, R., Rixon, M., Schou, O., Foley, K.P., Haugen, H., McMillen, S., Waggie, K., Schreckhise, R.W., Shoemaker, K., Vu, T., Moore, M., Grossman, A., Clegg, C.H. Immunity (2001) [Pubmed]
  8. Novel function of TNF cytokines in regulating bone marrow B cell survival. Zhang, M., Ko, K.H., Lam, Q.L., Lo, C.K., Xu, D.J., Shen, L., Zheng, B., Srivastava, G., Lu, L. Cell. Mol. Immunol. (2004) [Pubmed]
  9. A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses. Huntington, N.D., Tomioka, R., Clavarino, C., Chow, A.M., Liñares, D., Maña, P., Rossjohn, J., Cachero, T.G., Qian, F., Kalled, S.L., Bernard, C.C., Reid, H.H. Int. Immunol. (2006) [Pubmed]
  10. APRIL-deficient mice have normal immune system development. Varfolomeev, E., Kischkel, F., Martin, F., Seshasayee, D., Wang, H., Lawrence, D., Olsson, C., Tom, L., Erickson, S., French, D., Schow, P., Grewal, I.S., Ashkenazi, A. Mol. Cell. Biol. (2004) [Pubmed]
  11. BCMA is essential for the survival of long-lived bone marrow plasma cells. O'Connor, B.P., Raman, V.S., Erickson, L.D., Cook, W.J., Weaver, L.K., Ahonen, C., Lin, L.L., Mantchev, G.T., Bram, R.J., Noelle, R.J. J. Exp. Med. (2004) [Pubmed]
  12. Tight mucosal compartmentation of the murine immune response to antigens of the enteric microbiota. Konrad, A., Cong, Y., Duck, W., Borlaza, R., Elson, C.O. Gastroenterology (2006) [Pubmed]
  13. A synthetic peptide corresponding to amino acid residues 34 to 37 of human follicle-stimulating hormone beta-subunit accelerates the onset of puberty in male and female mice. Grasso, P., Rozhavskaya, M., Reichert, L.E. Endocrinology (1997) [Pubmed]
  14. APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Belnoue, E., Pihlgren, M., McGaha, T.L., Tougne, C., Rochat, A.F., Bossen, C., Schneider, P., Huard, B., Lambert, P.H., Siegrist, C.A. Blood (2008) [Pubmed]
  15. A role for B cell-activating factor of the TNF family in chemically induced autoimmunity. Zheng, Y., Gallucci, S., Gaughan, J.P., Gross, J.A., Monestier, M. J. Immunol. (2005) [Pubmed]
  16. B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Xu, S., Lam, K.P. Mol. Cell. Biol. (2001) [Pubmed]
  17. Field and laboratory studies on the timing of oviposition and hatching of the western black-legged tick, Ixodes pacificus (Acari: Ixodidae). Peavey, C.A., Lane, R.S. Exp. Appl. Acarol. (1996) [Pubmed]
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