IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides.
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.
Yi
A K
AK
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Chace
J H
JH
Cowdery
J S
JS
Krieg
A M
AM
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D018899:CpG Islands; D004269:DNA, Bacterial / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology
D004269:DNA, Bacterial; D007075:Immunoglobulin M; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D007371:Interferon-gamma