CD137 is induced by the CD40 signal on chronic lymphocytic leukemia B cells and transduces the survival signal via NF-κB activation

PLoS One. 2013 May 16;8(5):e64425. doi: 10.1371/journal.pone.0064425. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • CD40 Antigens / metabolism*
  • CD40 Ligand / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / agonists
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism*

Substances

  • CD40 Antigens
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • CD40 Ligand

Grants and funding

This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan (O.M.,T.F.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.