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

Abstract

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-κB (NF-κB)/Rel binding activities. An early transient increase in NF-κB/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-κB (IκB)-α, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF-κB/Rel factor binding and induced apoptosis. Bcl-X(L) expression protected WEHI 231 cells from apoptosis induced by these agents. Microinjection of WEHI 231 cells with either IκB-α-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-κB/Rel binding following anti-IgM treatment activates apoptosis of WEHI 231 cells; furthermore, they implicate the NF-κB/Rel family in control of apoptosis of normal and transformed B cells.