RT Journal
A1 Lai, Anne Y.
A1 Mav, Deepak
A1 Shah, Ruchir
A1 Grimm, Sara A.
A1 Phadke, Dhiral
A1 Hatzi, Katerina
A1 Melnick, Ari
A1 Geigerman, Cissy
A1 Sobol, Steve E.
A1 Jaye, David L.
A1 Wade, Paul A.
T1 DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation
JF Genome Research 
JO Genome Research 
YR 2013 
FD December 01 
VO 23 
IS 12 
SP 2030 
OP 2041 
DO 10.1101/gr.155473.113 
UL http://genome.cshlp.org/content/23/12/2030.abstract 
AB 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.