CD40 ligand, Bcl-2, and Bcl-xL spare group I Burkitt lymphoma cells from CD77-directed killing via Verotoxin-1 B chain but fail to protect against the holotoxin

Cell Death Differ. 2000 Sep;7(9):785-94. doi: 10.1038/sj.cdd.4400710.


Owing to its lineage and differentiation stage-restricted expression, CD77 has been mooted as a therapeutic target in Burkitt lymphoma (BL). The recognition that the globotriaosyl moiety of this neutral glycosphingolipid is a receptor for Escherichia coli-derived Verotoxin-1 (Shiga-Like Toxin-1) offers a potential delivery system for the attack. Here we show that CD77-expressing Group I BL cells which are normally susceptible to activation-induced death on binding Verotoxin-1 B chain are protected in the presence of CD40 ligand. Ectopic expression of either bcl-2 or bcl-xL also afforded resistance to the actions of the B chain. In total contrast, neither of the survival genes nor a CD40 signal - even when acting in concert - protected against killing mediated by the holotoxin. These findings indicate that while therapeutic modalities for CD77-expressing B cell tumors (which include follicular lymphoma) based on the use of Verotoxin-1 B chain might be compromised by the activation of endogenous or exogenous survival pathways, those exploiting the holotoxin should be left unscathed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Burkitt Lymphoma / drug therapy
  • Burkitt Lymphoma / metabolism*
  • Burkitt Lymphoma / pathology
  • CD40 Ligand / metabolism*
  • CD40 Ligand / pharmacology
  • Cell Death
  • Cell Line
  • DNA / metabolism
  • Escherichia coli / metabolism
  • Humans
  • Ionomycin / pharmacology
  • Protein Subunits
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Shiga Toxin 1 / metabolism
  • Shiga Toxin 1 / pharmacology*
  • Shiga Toxin 1 / therapeutic use
  • Signal Transduction
  • Trihexosylceramides / metabolism*
  • bcl-X Protein


  • Antibodies, Monoclonal
  • BCL2L1 protein, human
  • Protein Subunits
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cell Surface
  • Shiga Toxin 1
  • Trihexosylceramides
  • bcl-X Protein
  • CD40 Ligand
  • Ionomycin
  • globotriaosylceramide
  • DNA