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

• Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction [10].
• APRIL-deficient mice have normal immune system development [10].
• However, whether BAFF and APRIL are expressed in the bone marrow (BM) microenvironment and if these two cytokines modulate early B cell development remain unclear [8].
• Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes [11].
• Antigen-pulsed dendritic cells (DCs) stimulated production of specific IgA in the absence of T-cell help via costimulation by BAFF and/or APRIL, members of the TNF family [12].

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

• B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses [16].
• Replete females placed in the field on 2 December through to 8 March deposited eggs from 2 February through to 24 April; the eggs commenced hatching between 2 July and 21 August [17].

References