DNA methylome and transcriptome dynamics of human B and T cell memory during acute activation and proliferation.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B722
Abstract ID: 6004

Presenting Author:
Amit Singh , Staff Scientist at NIA, NIH

Abstract:

A cardinal feature of adaptive immunity to generate memory permits individuals to mount robust responses upon secondary encounter with pathogens. In this study, we explored epigenetics (DNA methylation) and transcriptomics at basal, activation and proliferation induced division states of naïve and memory B and CD4 T lymphocytes from human PBMC. We focused on the epigenetic changes that can recapitulate the naïve to memory differentiation. Any compelling evidence of epigenetics and transcriptomic relationship at resting state was absent. Activation by stimulating antigen receptor or PMA + ionomycin, identified: 126- B and 130- CD4 T cell genes (6 k-means clusters) that distinguished naïve and memory lymphocytes. However, both up- or down-regulated genes were hypomethylated during memory differentiation, indicating its non-selectivity in memory cells for accentuated expression. Proliferation related methylomes identified that human lymphocytes extensively re-organize their methylomes by active de- and re-methylation in response to mitogenic signals. This re-organization is distinct for B cells compared to CD4 T cells. Divided CD4 T cells can recapitulate ARNT, bZIP and NF-κB transcription factor motifs of memory-associated hypomethylated DNA. This ex vivo cell division partially mimicked gene expression changes associated with CD4 T cell, but not B cell, memory generation. Our findings provide molecular features to understand human adaptive memory differentiation and function.