CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of I kappa B alpha and I kappa B beta and sustained activation of nuclear factor-kappa B/c-Rel.

Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFkappaB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFkappaB activation. Anti-IgM induced IkappaB alpha degradation followed by increased IkappaB alpha protein levels. The levels of IkappaB beta were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IkappaB alpha and IkappaB beta degradation in the presence or absence of anti-IgM. Inhibition of IkappaB degradation blocked CpG DNA-induced NFkappaB activation and expression of c-myc. Prevention of NFkappaB activation by inhibiting IkappaB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM-induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFkappaB depends on the degradation of IkappaB alpha and IkappaB beta and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.