title: CpG DNA redirects class-switching towards "Th1-like" Ig isotype production via TLR9 and MyD88.
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.
authors.affiliation: Department of Internal Medicine/Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Gerth
authors.forename: Stanford L
authors.initials: SL
authors.lastname: Peng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D018899:CpG Islands / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9