Lymphocyte recognition of characteristic structural features in microbial DNA 
may contribute to immune defense by promoting protective immune responses. The 
dinucleotide CpG is significantly under-represented in vertebrate DNA and is 
usually methylated. In contrast, CpG dinucleotides are generally present at the 
expected frequency in bacterial DNA and are unmethylated. These unmethylated CpG 
motifs induce B cells to secrete IL-6 and IgM, and can induce NK and CD4+ T 
cells to produce the immunoregulatory Th1 cytokine, IFN-gamma. IFN-gamma 
inhibits IgM secretion that is triggered by a different bacterial product, LPS. 
The present study demonstrates that in contrast to its antagonistic interaction 
with LPS, IFN-gamma causes a dose-dependent increase in the level of IgM 
secretion induced by CpG DNA. Like IgM secretion, B cell secretion of IL-6 more 
than doubles after the addition of exogenous IFN-gamma. Mice with disrupted 
IFN-gamma genes produced less than half as much IL-6 and IgM in response to CpG 
DNA, supporting the hypothesis that CpG-induced IFN-gamma production contributes 
to the B cell response. In contrast to its promotion of IL-6 and IgM secretion, 
IFN-gamma did not significantly affect the spleen cell proliferation activated 
by CpG motifs. These results indicate that IFN-gamma produced by T and NK cells 
after CpG DNA stimulation contributes to the B cell production of IL-6 and the 
subsequent Ig production. These studies provide further evidence that the immune 
system responds to CpG motifs in bacterial DNA by activating a coordinated set 
of humoral and cellular responses.