Article

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: 2.69). 01/2000; 380(12):1443-7. DOI: 10.1515/BC.1999.186
Source: PubMed

ABSTRACT 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.

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    • "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]. "
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    • "B lymphocyte stimulator (BLyS, also designated TALL-1, THANK, BAFF, TNFSF13b, and TNFSF20) is a member of the tumor necrosis factor superfamily of ligands [1,2]. BLyS is expressed by activated T cells, activated macrophages, and dendritic cells [1,3,4] and has been implicated in autoimmune disorders characterized by the presence of pathological concentrations of self-antigen-reactive antibodies, such as systemic lupus erythematosus (SLE) [5] and rheumatoid arthritis (RA) [6]. Biological activity of BLyS is mediated via three receptors present on B and T cells designated transmembrane activator and calcium-modulator and cyclophilin ligand [CAML] interactor (TACI), B-Cell Maturation Antigen (BCMA) and BAFF Receptor (BR3 or BAFF-R) [7]. "
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