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*
Interdisciplinary Graduate Program in Immunology and Department of Internal Medicine, University of Iowa College of Medicine, and
University of Iowa College of Pharmacy, Iowa City, IA 52242; and
Department of Veteran Affairs Medical Center, Iowa City, IA 52246
B cells and monocytes endocytose DNA into an acidified
intracellular compartment. If this DNA contains unmethylated CpG
dinucleotides in particular base contexts (CpG motifs), these
leukocytes are rapidly activated. We now show that both B cell and
monocyte-like cell line responses to DNA containing CpG motifs (CpG
DNA) are sensitive to endosomal acidification inhibitors; they are
completely blocked by bafilomycin A, chloroquine, and monensin. The
specificity of these inhibitors is demonstrated by their failure to
prevent responses to LPS, PMA, or ligation of CD40 or IgM.
Acidification of endosomal CpG DNA is coupled to the rapid generation
of intracellular reactive oxygen species. The CpG DNA-induced reactive
oxygen species burst is linked to the degradation of I
B and the
activation of NFB, which induces leukocyte gene transcription and
cytokine secretion. These studies demonstrate a novel pathway of
leukocyte activation triggered by CpG motifs.
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