Mitogenicity of DNA from different organisms for murine B cells

Recent evidence that DNA from bacteria causes polyclonal activation of mouse B cells raises the question of whether DNA from other organisms has similar properties. Extending prior studies on bacteria and insects, we show here that the capacity of DNA to stimulate B cells correlates closely with hypomethylation of DNA CpG dinucleotide motifs. Thus strong stimulation of B cells was seen with DNA from various organisms displaying little or no methylation of CpG motifs, i.e., yeast, nematodes, and molluscs in addition to bacteria and insects. For these organisms, DNA induced nearly all B cells (including small resting B cells) to up-regulate the activation marker, CD69, and caused many B cells to enter the cell cycle, indicative of polyclonal activation; this effect was not seen after selective methylation of CpG motifs (tested on yeast DNA). By contrast, no stimulation of B cells was seen with DNA from organisms whose CpG motifs are heavily methylated, i.e., various vertebrates (mammals, fish, and frogs) and plants (corn). Despite this correlation, DNA prepared from two murine cell lines exhibiting hypomethylation of CpG motifs caused little or no stimulation of B cells. Thus, the idea that the stimulatory properties of DNA correlate solely with the presence of unmethylated CpG motifs may be an oversimplification.