CpG DNA redirects class-switching towards "Th1-like" Ig isotype production via TLR9 and MyD88.
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.
Lin
Ling
L
Department of Internal Medicine/Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gerth
Andrea J
AJ
Peng
Stanford L
SL
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
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