CpG DNA induces a class II transactivator-independent increase in class II MHC by stabilizing class II MHC mRNA in B lymphocytes.
Microbial products, such as CpG DNA and LPS, enhance class II MHC (MHC-II) expression and Ag presentation by dendritic cells, but this effect does not occur with macrophages and is largely unexplored in B cells. Although MHC-II expression is influenced by transcriptional regulation, which is governed by class II transactivator (CIITA) in all cells, microbial products enhance MHC-II expression by dendritic cells in part by increasing MHC-II protein stability. In this study, we show that the CpG-induced increase in MHC-II expression by B lymphocytes is not due to protein stabilization or changes in CIITA expression or activity, but instead is due to increased stability of MHC-II mRNA. This CIITA-independent mechanism adds a new layer of complexity to regulation of MHC-II and may increase T cell help for B cell Ab responses to microbial or vaccine Ags.
Kuchtey
John
J
Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Pennini
Meghan
M
Pai
Rish K
RK
Harding
Clifford V
CV
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D007399:Interphase / Q000276:immunology; D051917:Leukosialin; D051379:Mice; D008809:Mice, Inbred C3H; D009113:Muramidase / Q000378:metabolism; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D020871:RNA Stability / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; C408982:CPG-oligonucleotide; D000949:Histocompatibility Antigens Class II; D051917:Leukosialin; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D015534:Trans-Activators; C400524:hen egg lysozyme peptide (48-61); D009113:Muramidase