Cell-penetrating anti-native DNA antibodies trigger apoptosis through both the neglect and programmed pathways.

It has been previously shown that certain antibodies to double stranded-DNA are capable to transgress the cell membrane, translocate to the cell nucleus and react with their antigens. When so doing, they signal the penetrated cells to undergo apoptosis. In this study we dissected the two main-streams of apoptotic triggering and found that the neglect, mitochondrial pathway, is definitely involved, but activation of caspases 2 and 8, classically known to be associated to the membrane pathway, also occurs in a small proportion of cells. Our results suggest that penetrating anti-dsDNA antibodies, besides activating neglect apoptosis, may also trigger programmed cell death, perhaps initiated at the cell membrane level.