Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells.
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.
Department of Biochemistry, Boston University School of Medicine, MA 02118, USA.
M
M
Wu
H
H
Lee
R E
RE
Bellas
S L
SL
Schauer
M
M
Arsura
D
D
Katz
M J
MJ
FitzGerald
T L
TL
Rothstein
D H
DH
Sherr
G E
GE
Sonenshein
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology*; D007075:Immunoglobulin M / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000473:pathology; D051379:Mice; D008845:Microinjections; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000473:pathology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D007075:Immunoglobulin M; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C497594:Relb protein, mouse; D014157:Transcription Factors; D051020:bcl-X Protein; D051841:Transcription Factor RelB; D014108:Tosylphenylalanyl Chloromethyl Ketone