title: CD137 is induced by the CD40 signal on chronic lymphocytic leukemia B cells and transduces the survival signal via NF-κB activation.
abstract: CD137 is a member of the tumor necrosis factor receptor family that is expressed on activated T cells. This molecule provides a co-stimulatory signal that enhances the survival, and differentiation of cells, and has a crucial role in the development of CD8 cytotoxic T cells and anti-tumor immunity. Here we report that CD137 expression is also induced on normal or malignant human B cells by CD40 ligation by its ligand CD154. This CD137 induction was more prominent in chronic lymphocytic leukemia (CLL) cells than in other types of B cells. CD137 stimulation on B cells by its ligand induced the nuclear translocation of p52 (a non-canonical NF-κB factor). In agreement with this finding, expression of the survival factor BCL-XL was upregulated. Consequently, the CD137 signal augmented the survival of CD154-stimulated CLL B cells in vitro. This unexpected induction of CD137 on B cells by CD40 signal may influence the clinical course of CLL.
authors.affiliation: Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yukana
authors.initials: Y
authors.lastname: Nakaima
authors.forename: Ken
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Koyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D023201:CD40 Ligand