Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis

EMBO J. 1995 Dec 15;14(24):6136-47.

Abstract

Activation of the cell surface receptor Fas/APO-1 (CD95) induces apoptosis in lymphocytes and regulates immune responses. The cytoplasmic membrane protein Bcl-2 inhibits lymphocyte killing by diverse cytotoxic agents, but we found it provided little protection against Fas/APO-1-transduced apoptosis in B lymphoid cell lines, thymocytes and activated T cells. In contrast, the cowpox virus protease inhibitor CrmA blocked Fas/APO-1-transduced apoptosis, but did not affect cell death induced by gamma-radiation or serum deprivation. Signalling through Fas/APO-1 did not down-regulate Bcl-2 or induce its antagonists Bax and Bcl-xS. In Fas/APO-1-deficient lpr mice, Bcl-2 transgenes markedly augmented the survival of antigen-activated T cells and the abnormal accumulation of lymphocytes (although they did not interfere with deletion of auto-reactive cells in the thymus). These data raise the possibility that Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Apoptosis / physiology*
  • Autoimmunity
  • Base Sequence
  • Cell Line
  • DNA Primers / genetics
  • Gene Expression
  • Humans
  • Lymphatic Diseases / etiology
  • Lymphocyte Activation
  • Lymphocytes / cytology*
  • Lymphocytes / immunology
  • Lymphocytes / physiology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes
  • Serpins / physiology
  • Signal Transduction / physiology
  • T-Lymphocytes / immunology
  • Viral Proteins*
  • fas Receptor / genetics
  • fas Receptor / physiology*

Substances

  • DNA Primers
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Serpins
  • Viral Proteins
  • fas Receptor
  • interleukin-1beta-converting enzyme inhibitor