CpG DNA rescues B cells from apoptosis by activating NF kappa B and preventing mitochondrial membrane potential disruption via a chloroquine sensitive pathway

Isolated murine splenic a cells gradually undergo spontaneous apoptosis whi le WEHI-231 a lymphoma cells undergo activation-induced apoptosis, Unmethyl ated CpG dinucleotides in a particular sequence context (CpG motif) in bact erial DNA or in synthetic oligodeoxynucleotides (CpG DNA) rescue both splen ic a cells and WEHI-231 cells from apoptosis, an effect which could potenti ally contribute to autoimmune disease. Chloroquine has; been used as an eff ective therapeutic agent for some autoimmune diseases, although the mechani sm of action is riot clearly understood. Low concentrations of chloroquine (<5 mu M) selectively abolished CpG DNA-mediated protection against spontan eous apoptosis of splenic a cells and against anti-IgM-induced apoptosis of WEHI-231 cells without affecting anti-apoptotic activities of anti-CD40 or lipopolsaccharide. CpG DNA effectively prevented mitochondrial membrane po tential disruption through a chloroquine-sensitive pathway in splenic B cel ls, Apoptosis protection by CpG DNA was also associated with increased expr ession of several proto-oncogenes and oncoproteins directly and/or indirect ly through a rapid and sustained activation of NF kappa B in splenic a cell s and WEHI-231 cells, These effects were also suppressed by chloroquine, Ou r results suggest that despite the difference in maturation phenotype of sp lenic a cells and WEHI-231 cells, CpG DNA rescues both from apoptosis by si milar pathway, which is blocked at an early step by chloroquine.