DNA Methylation and Immune Memory Response

Abstract

The generation of memory is a cardinal feature of the adaptive immune response, involving different factors in a complex process of cellular differentiation. This process is essential for protecting the second encounter with pathogens and is the mechanism by which vaccines work. Epigenetic changes play important roles in the regulation of cell differentiation events. There are three types of epigenetic regulation: DNA methylation, histone modification, and microRNA expression. One of these epigenetic changes, DNA methylation, occurs in cytosine residues, mainly in CpG dinucleotides. This brief review aimed to analyse the literature to verify the involvement of DNA methylation during memory T and B cell development. Several studies have highlighted the importance of the DNA methyltransferases, enzymes that catalyse the methylation of DNA, during memory differentiation, maintenance, and function. The methylation profile within different subsets of naïve activated and memory cells could be an interesting tool to help monitor immune memory response.

Keywords: B cells; DNA methylation; T cells; epigenetic; memory response.

Figure 1

DNA methylation and memory CD4 T cell: memory CD4 T cells are generated following activation of naïve T cell by dendritic cell presenting peptide on major histocompatibility complex (MHC) molecules. FOXP1 is a transcriptional factor that controls memory differentiation and is regulated by DNA methylation. There is a progressive loss of DNA methylation during memory differentiation. DNA methylation of Gzmb gene can be used as a marker to distinguish memory CD4 Th1 from Tfh. The expression of Foxp3 in memory Treg is controlled by DNA methylation at TSDR (Treg cell-specific demethylation region).

Figure 2

DNA methylation and memory CD8 T cell: memory CD8 T cells presented a decreased DNA methylation of granzyme, perforin, IFN-gamm and CX3CR1 genes.

Figure 3

DNA methylation and memory B cell: A—differentiation of naïve B cells into short-lived plasma cells and germinal centre (GC) B cells. B—differentiation of GC B cells into long-lived plasma cells and secondary memory B cells. This process occurs in lymphoid organs in the B cell follicles and the germinal centres. The transition from naïve to GC B cell is dominated by loss of methylation in immune activation-induced DNA methylation regions.