Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells

EMBO J. 1996 Sep 2;15(17):4682-90.


Apoptosis of the WEHI 231 immature B cell lymphoma line following membrane interaction with an antibody against the surface IgM chains (anti-IgM) is preceded by dramatic changes in Nuclear Factor-kappaB (NF-kappaB)/ Rel binding activities. An early transient increase in NF-kappaB/Rel binding is followed by a significant decrease in intensity below basal levels. Here we have explored the role of these changes in Rel-related factors in B cell apoptosis. Treatment of WEH1 231 cells with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a protease inhibitor which prevents degradation of the inhibitor of NF-kappaB (IkappaB)-alpha, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF-kappaB/Rel factor binding and induced apoptosis. Bcl-XL expression protected WEHI 231 cells from apoptosis induced by these agents. Microinjection of WEHI 231 cells with either IkappaB-alpha-GST protein or a c-Rel affinity-purified antibody induced apoptosis. Ectopic c-Rel expression ablated apoptosis induced by TPCK or anti-IgM. Treatment of BALENLM 17 and A20 B lymphoma cells or normal murine splenic B lymphocytes with either TPCK or PDTC also resulted in apoptosis. These findings indicate that the drop in NF-kappaB/Rel binding following anti-IgM treatment activates apoptosis of WEHI 231 cells; furthermore, they implicate the NF-kappaB/Rel family in control of apoptosis of normal and transformed B cells.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • B-Lymphocytes / pathology*
  • Immunoglobulin M / drug effects
  • Lymphoma, B-Cell / pathology
  • Mice
  • Microinjections
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Spleen / pathology
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology
  • Transcription Factor RelB
  • Transcription Factors*
  • Tumor Cells, Cultured
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • Immunoglobulin M
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Relb protein, mouse
  • Transcription Factors
  • bcl-X Protein
  • Transcription Factor RelB
  • Tosylphenylalanyl Chloromethyl Ketone