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IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides.

A K Yi, J H Chace, J S Cowdery and A M Krieg
J Immunol January 15, 1996, 156 (2) 558-564;
A K Yi
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J H Chace
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J S Cowdery
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A M Krieg
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Abstract

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.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 156, Issue 2
15 Jan 1996
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IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides.
A K Yi, J H Chace, J S Cowdery, A M Krieg
The Journal of Immunology January 15, 1996, 156 (2) 558-564;

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IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides.
A K Yi, J H Chace, J S Cowdery, A M Krieg
The Journal of Immunology January 15, 1996, 156 (2) 558-564;
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Print ISSN 0022-1767        Online ISSN 1550-6606