Characterization of a New Member of the TNF Family Expressed on Antigen Presenting Cells

Chiron Corporation, Emeryville, CA 94608-2916, USA.
Biological Chemistry (Impact Factor: 3.27). 01/2000; 380(12):1443-7. DOI: 10.1515/BC.1999.186
Source: PubMed


The TNF family is involved in the regulation of the immune system, and its members have been implicated in a variety of biological events such as apoptosis, cell proliferation, differentiation and survival. Here we present a new member of the TNF family, tumor necrosis factor superfamily member 20 (TNFSF20) that we have identified from the expressed sequence tag (EST) database and characterized. The human protein is a 285 amino acid long type II transmembrane protein and is 19% homologous to TNF in its extra-cellular domain. TNFSF20 is expressed at the surface of antigen presenting cells such as cells of the macrophagemonocyte lineage and dendritic cells. After treatment with bacterial lipopolysaccharide (LPS), TNFSF20 expression is downregulated at the surface of the expresssing cells, suggesting that the membrane-bound protein gets cleaved, and that a soluble factor is released in the extra-cellular compartment. The soluble form of the recombinant TNFSF20 induces proliferation of resting peripheral blood monocytes (PBMC) and cell death of activated lymphocytes. TNFSF20 might therefore play a critical role in the regulation of cell-mediated immune responses.

51 Reads
  • Source
    • "The B-cell activating factor of the TNF family (BAFF, also known as BLyS, TALL-1, THANK, zTNF4, and TNFSF13b) is a 285-amino acid transmembrane protein that exists in both membrane and cleaved 152-amino-acid soluble forms (Moore et al., 1999; Mukhopadhyay et al., 1999; Schneider et al., 1999; Shu et al., 1999; Tribouley et al., 1999; Gross et al., 2000) and plays major roles in B-cell survival, proliferation, and differentiation (Rolink et al., 2002). BAFF is a type II transmembrane protein that forms biologically active trimers (Bodmer et al., 2002). "

  • Source
    • "The soluble region of BAFF is designated the D-E loop, or " Flap " , and contains conserved cysteine (Cys) residues and N-glycosylation sites. Three types of B cell receptors are involved in mediating the in vivo activity of BAFF: B cell maturation antigen (BCMA), trans-membrane activator and CAML interactor (TACI), and BAFF receptor (BAFFR) (Gross et al., 2000; Schneider et al., 1999; Tribouley et al., 1999). Of these, BAFFR is the principal receptor for BAFF (Liang et al., 2010), while BCMA and TACI possess higher potential for binding to other TNF family ligand members (Bossen and Schneider, 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) ligand family. BAFF has been shown to induce survival and proliferation of lymphocytes. We characterized the gene encoding BAFF (RbBAFF) in rock bream (Oplegnathus fasciatus), and attempted to determine its biological functions upon immune responses. In silico analysis of RbBAFF demonstrated the presence of common TNF ligand family features, including a TNF domain, a D-E loop, and three cysteine residues that are crucial for trimer formation. Amino acid sequence alignment confirmed that RbBAFF and its homologs were conserved at secondary and tertiary levels. Transcriptional analysis indicated that RbBAFF mRNAs were ubiquitously expressed in wide array of tissues. The higher levels of constitutive expression were observed in the kidney, head kidney and spleen, suggesting an important physiological relationship with lymphocytes. Under pathological conditions, RbBAFF mRNA levels were significantly elevated. The role of RbBAFF in lymphocyte survival and proliferation was confirmed by MTT assays and flow cytometry. Recombinant RbBAFF protein (10 μg/mL) was able to prolong the survival and/or enhance the proliferation of rock bream lymphocytes by approximately 30%. Transcription of IL-10 and NFκB-1 was significantly stimulated by RbBAFF. Our findings provide further information regarding fish BAFF gene and its role in adaptive immunity.
    Developmental and comparative immunology 10/2015; 55. DOI:10.1016/j.dci.2015.10.004 · 2.82 Impact Factor
  • Source
    • "B-cell-activating factor of the TNF family (BAFF) (tumor necrosis factor ligand superfamily, member 13b) is a cytokine which is primarily produced by monocytes and dendritic cells [2-4] in addition to T cells [5,6]. It plays a crucial role in the proliferation, differentiation and survival of B cells [2,4,5,7]. BAFF is a type II membrane-bound protein of 285 amino acid residues. A C-terminal fragment of 152 amino acid residues is released from cells as soluble BAFF (sBAFF) [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated possible aberrations of monocytes from patients with primary Sjögren's syndrome (pSS). We focused on B-cell-activating factor of the TNF family (BAFF) and IL-6 because they are both produced by monocytes and are known to be involved in the pathogenesis of pSS. Peripheral monocytes were prepared from both pSS patients and normal individuals. The cells were stimulated in vitro with IFN-γ, and the amounts of IL-6 and soluble BAFF (sBAFF) produced by the cells were quantitated. The effect of sBAFF itself on the production of IL-6 was also studied. To investigate the response of pSS monocytes to these stimuli, the expression levels of the genes encoding BAFF receptors and IL-6-regulating transcription factors were quantitated. Peripheral pSS monocytes produced significantly higher amounts of sBAFF and IL-6 than normal monocytes did, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-γ. The elevated production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of pSS monocytes with sBAFF induced a significant increase in IL-6 production. Moreover, the expression levels of a BAFF receptor and transcription factors regulating IL-6 were significantly elevated in pSS monocytes compared to normal monocytes. The results of the present study suggest that the mechanisms underlying the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is due to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may cause the development of pSS.
    Arthritis research & therapy 10/2011; 13(5):R170. DOI:10.1186/ar3493 · 3.75 Impact Factor
Show more

Similar Publications