CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway

J Exp Med. 1995 Nov 1;182(5):1557-65. doi: 10.1084/jem.182.5.1557.


The Apo-1/Fas antigen (CD95) mediates programmed cell death of lymphocytes when bound by Fas ligand or anti-Apo-1/Fas antibody. In contrast, the CD40 antigen provides a potent activation and survival signal to B lymphocytes when it is engaged by its T cell ligand (CD40L, gp39) or cross-linked by anti-CD40 antibody. In this study, we use human tonsillar B cells and the Ramos Burkitt's lymphoma B cell line, which serves as a model for human germinal center B lymphocytes, to study the effectors of Apo-1/Fas expression and apoptosis of human B cells. We found that Apo-1/Fas expression was upregulated on both malignant and normal human B lymphocytes after CD40 ligation induced by (a) cognate T helper-B cell interaction mediated by microbial superantigen (SAg); (b) contact-dependent interaction with CD40L+, but not CD40L- Jurkat mutant T cell clones; and (c) monoclonal anti-CD40, but not any of a panel of control antibodies. Enhanced B cell Fas/Apo-1 expression is functionally significant. Coculture of Ramos Burkitt's lymphoma line cells with irradiated SAg-reactive CD4+ T cells with SAg or CD40L+ Jurkat T cells results in B cell apoptosis, evidenced by reduced cell viability and DNA laddering. This process is augmented by the addition of anti-Apo-1/Fas monoclonal antibody, consistent with an acquired susceptibility to Apo-1/Fas-mediated apoptosis. These data support an immunoregulatory pathway in which seemingly contradictory signals involving the B cell proliferation/survival antigen CD40, as well as the Apo-1/Fas molecule, which mediates programmed cell death of lymphocytes, are linked in the process of human B cell activation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / physiology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Burkitt Lymphoma / pathology
  • CD40 Antigens / physiology*
  • CD40 Ligand
  • Cells, Cultured
  • DNA Damage
  • DNA, Neoplasm / analysis
  • Fas Ligand Protein
  • Gene Expression Regulation
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Lymphocyte Activation
  • Membrane Glycoproteins / pharmacology
  • Membrane Glycoproteins / physiology*
  • Palatine Tonsil / cytology
  • Tumor Cells, Cultured
  • fas Receptor / biosynthesis*
  • fas Receptor / genetics
  • fas Receptor / immunology


  • Antibodies, Monoclonal
  • CD40 Antigens
  • DNA, Neoplasm
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • fas Receptor
  • CD40 Ligand