CPG DNA RESCUE OF MURINE-B LYMPHOMA-CELLS FROM ANTI-IGM-INDUCED GROWTH ARREST AND PROGRAMMED CELL-DEATH IS ASSOCIATED WITH INCREASED EXPRESSION OF C-MYC AND BCL-X(L)

One of the principal mechanisms thought to maintain B cell tolerance t o self Ags is deletion of cells bearing functional IgM receptors for s elf Ag via apoptosis in the bone marrow, Because of ifs characteristic growth arrest and apoptosis in response to surface IgM cross-linking, the B cell line WEHl-231 has been a useful model system for studies o f Ag receptor-mediated apoptosis, Unmethylated CpG dinucleotides in ol igonucleotides (CpG DNA) can be strong B cell mitogens, In the present study we evaluated whether CpG DNA can rescue WEHI-231 cells from ant i-lgM-induced cell cycle arrest and apoptosis, The addition of CpG DNA protected WEHI-231 cells from anti-IgM-mediated apoptosis as well as growth arrest, The protective effect of CpG DNA was dependent on the p resence of unmethylated CpG dinucleotides. Kinetic analyses showed tha t the addition of CpG DNA can be delayed for up to 3 h after anti-lgM treatment with no decrease in the protection, CpG DNA reversed anti-lg M-induced down-regulation of c-myc expression in WEHI-231 and up-regul ated myn, bcl(2) and bcl=x(L) mRNA expression. Our results suggest tha t CpG DNA protection of WEHI-231 cells from anti-lgM-induced apoptosis may he mediated by specific and/or cooperative interactions of multip le genes and that CpG DNA could be a useful tool for studies of B cell tolerance.