title: DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation.
abstract: Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized. Here we profile the DNA methylome and the transcriptome of B-lymphocyte subsets representing stages of the humoral immune response before and after antigen exposure in vivo from multiple humans. A significant percentage of activation-induced losses of DNA methylation mapped to transcription factor binding sites. An additional class of demethylated loci mapped to Alu elements across the genome and accompanied repression of DNA methyltransferase 3A. The activation-dependent DNA methylation changes were largely retained in the progeny of activated B cells, generating a similar epigenetic signature in downstream memory B cells and plasma cells with distinct transcriptional programs. These findings provide insights into the methylation dynamics of the genome during cellular differentiation in an immune response.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA;
authors.forename: Anne Y
authors.initials: AY
authors.lastname: Lai
authors.forename: Deepak
authors.initials: D
authors.lastname: Mav
authors.forename: Ruchir
authors.initials: R
authors.lastname: Shah
authors.forename: Sara A
authors.initials: SA
authors.lastname: Grimm
authors.forename: Dhiral
authors.initials: D
authors.lastname: Phadke
authors.forename: Katerina
authors.initials: K
authors.lastname: Hatzi
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Cissy
authors.initials: C
authors.lastname: Geigerman
authors.forename: Steve E
authors.initials: SE
authors.lastname: Sobol
authors.forename: David L
authors.initials: DL
authors.lastname: Jaye
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wade
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D020087:Alu Elements; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C000717967:DNMT3A protein, human; D014157:Transcription Factors; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A