|4‑1BB Ligand/TNFSF9 in Human Placenta. 4‑1BB Ligand/TNFSF9 was detected in immersion fixed paraffin-embedded sections of human placenta using Goat Anti-Human 4‑1BB Ligand/TNFSF9 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF2295) at 1 µg/mL for 1 hour at room temperature followed by incubation with the Anti-Goat IgG VisUCyte™ HRP Polymer Antibody (Catalog # VC004). Tissue was stained using DAB (brown) and counterstained with hematoxylin (blue). Specific staining was localized to syncytiotrophoblasts. View our protocol for IHC Staining with VisUCyte HRP Polymer Detection Reagents.|
4-1BB ligand (4-1BBL; also CD137L) is a 32 kDa type II transmembrane protein that belongs to the TNF superfamily (TNFSF) molecules (1‑4). The human 4-1BBL cDNA encodes a 254 amino acid (aa) protein that contains a 25 aa N-terminal cytoplasmic domain, a 23 aa transmembrane segment, and a 206 aa C-terminal extracellular region (5). The extracellular domain (ECD) of 4-1BBL has a jelly-roll, beta -sandwich tertiary structure that is similar to other TNFSF members. There is only one cysteine in the human ECD, and no potential N-linked glycosylation sites. The potential exists, however, for O-linked glycosylation. The human 4-1BBL ECD shares 32% and 35% aa identity with mouse and rat ECD, respectively. In the cytoplasmic domain, human 4-1BBL is 55 aa shorter than the equivalent region in rodents. 4-1BBL is expressed by activated B cells, macrophages, dendritic cells, activated T cells, neurons and astrocytes (2, 3, 6). A 26 kDa soluble form of 4-1BBL is known to occur in humans. Although it is presumably generated by MMP activity, its amino acid size is currently unreported (4). The soluble form is bioactive. Human 4-1BBL signals through both CD137/4-1BB and itself. Its cytoplasmic tail participates in reverse signaling that induces apoptosis in T cells and cytokine secretion (IL-6; TNF-alpha ) by monocytes (7, 8). 4-1BBL binding to CD137/4-1BB produces a number of effects. It seems to play a key role in the T cell recall response. It maintains T cell numbers at the end of a primary response, and induces CD4+ and CD8+ T cells to proliferate and secrete cytokines such as IL-2 and IFN-gamma in CD4+ cells, and IFN-gamma in CD8+ cells (9, 10).
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