Abstract
Unmethylated CpG-containing DNA plays a critical role in immunity via the augmentation of Th1 but suppression of Th2 T cell responses. We describe here that CpG motifs also redirect isotype production by murine B cells to "Th1-like" Ig isotypes (IgG2a, IgG2b, and IgG3) while suppressing Th2 isotypes (IgG1 and IgE). Using genetically mutant B cells, we find that the IgG2a, IgG2b and IgG3 isotypes are transcriptionally regulated via the promotion of class-switching, in a manner critically dependent upon TLR9 and MyD88. Thus, CpG DNA redirects Ig isotype production by regulating the specificity of class-switch recombination.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, Differentiation / metabolism*
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CpG Islands / physiology*
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DNA-Binding Proteins / metabolism*
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Immunoglobulin Class Switching / genetics
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Immunoglobulin Class Switching / immunology
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Immunoglobulin Class Switching / physiology*
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Immunoglobulins / biosynthesis
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Immunoglobulins / genetics*
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Immunoglobulins / immunology
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Mice
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Myeloid Differentiation Factor 88
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Receptors, Cell Surface / metabolism*
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Receptors, Immunologic / metabolism*
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Th1 Cells / immunology
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Toll-Like Receptor 9
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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DNA-Binding Proteins
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Immunoglobulins
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Cell Surface
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Receptors, Immunologic
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Tlr9 protein, mouse
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Toll-Like Receptor 9