|Detection of 4‑1BB Ligand/TNFSF9 in A20 Mouse Cell Line by Flow Cytometry. A20 mouse B cell lymphoma cell line was stained with Rat Anti-Mouse 4‑1BB Ligand/TNFSF9 Fluorescein‑conjugated Monoclonal Antibody (Catalog # FAB1246F, filled histogram) or isotype control antibody (Catalog # IC013F, open histogram). View our protocol for Staining Membrane-associated Proteins.|
4-1BB ligand (4-1BBL) is a type II transmembrane glycoprotein belonging to the TNF superfamily (TNFSF) and has been designated TNFSF9. Mouse 4-1BBL cDNA encodes a 309 amino acid residues (aa) protein with an 82 aa N-terminal cytoplasmic domain, a 21 aa transmembrane domain and a 206 aa C-terminal extracellular domain. The extracellular domain of 4-1BBL has a tertiary structure similar to that of other TNFSF members, but shares only low aa sequence homology (14‑16%). Murine 4-1BBL shares 36% aa sequence identity with its human counterpart (1, 2). 4-1BBL is predominantly expressed on activated antigen presenting cells (APCs) such as B cells, macrophages and dendritic cells (DCs). It is also expressed on most T and B lymphoma cell lines (3). A soluble 4-1BBL is released from the cell surface following cellular activation via proteolytic cleavage by one or more sheddases (4). By analogy to other TNFSF ligands, both the soluble and transmembrane 4-1BBL are expected to exist as non-covalent homotrimers. 4-1BBL binds 4-1BB, a TNF receptor superfamily member, TNFRSF9, which is also known as CD137 and ILA (induced by lymphocyte activation). 4-1BB is expressed on activated CD4+ and CD8+ T cells, thymocytes, and NK cells. It is also expressed on monocytes, neutrophils, DCs and eosinophils. In response to 4-1BBL binding, 4-1BB transduces a T cell costimulatory signal in both CD4+ and CD8+ T cells to promote survival and enhance proliferation, cytokine production and effector function. In dendritic cells, 4-1BB is a DC-activating molecule that enhances cytokine production and upregulates expression of B7-1 and B7-2 costimulatory molecules (3).