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. 2022 Dec 15;14(1):173.
doi: 10.1186/s13148-022-01399-0.

Comparative analysis of the DNA methylation landscape in CD4, CD8, and B memory lineages

Ze Zhang  1 , Rondi Butler  2 , Devin C Koestler  3 , Shelby Bell-Glenn  3 , Gayathri Warrier  4 , Annette M Molinaro  4 , Brock C Christensen  1   5 , John K Wiencke  4 , Karl T Kelsey #  6 , Lucas A Salas #  7   8
Affiliations

Comparative analysis of the DNA methylation landscape in CD4, CD8, and B memory lineages

Ze Zhang et al. Clin Epigenetics. .

Abstract

Background: There is considerable evidence that epigenetic mechanisms and DNA methylation are critical drivers of immune cell lineage differentiation and activation. However, there has been limited coordinated investigation of common epigenetic pathways among cell lineages. Further, it remains unclear if long-lived memory cell subtypes differentiate distinctly by cell lineages.

Results: We used the Illumina EPIC array to investigate the consistency of DNA methylation in B cell, CD4 T, and CD8 T naïve and memory cells states. In the process of naïve to memory activation across the three lineages, we identify considerable shared epigenetic regulation at the DNA level for immune memory generation. Further, in central to effector memory differentiation, our analyses revealed specific CpG dinucleotides and genes in CD4 T and CD8 T cells with DNA methylation changes. Finally, we identified unique DNA methylation patterns in terminally differentiated effector memory (TEMRA) CD8 T cells compared to other CD8 T memory cell subtypes.

Conclusions: Our data suggest that epigenetic alterations are widespread and essential in generating human lymphocyte memory. Unique profiles are involved in methylation changes that accompany memory genesis in the three subtypes of lymphocytes.

Keywords: B cell; CD4 T cell; CD8 T cell; Central memory cell; DNA methylation; Effector memory cell; Immune activation; Immune response; TEMRA.

PubMed Disclaimer

Conflict of interest statement

Drs. Kelsey and Wiencke are founders of Cellintec, which had no role in this research.

Figures

Fig. 1
Fig. 1
Top 20 significant differentially methylation CpGs between naïve and memory cells ranked by |Δ Beta| with their respective genes in B cell, CD4, and CD8 lineages
Fig. 2
Fig. 2
Shared differentially methylation CpGs between naïve and memory cells across B cell, CD4, and CD8 lineages. a Venn diagram demonstrating 15 out of 100 compared loci were in shared memory generation for all lineages. b Heatmap demonstrating methylation profile in 15 shared CpGs between naïve and memory cells across lineages
Fig. 3
Fig. 3
Heatmap of the methylation profile of the ATE1 gene, demonstrating specific regions that are methylated in all subtypes of naïve cells but are demethylated in memory cells across B cell, CD4, and CD8 lineages
Fig. 4
Fig. 4
Significantly enriched GO biological processes with genes associated with shared differentially methylation CpGs between naïve and memory cells in the B cell, CD4, and CD8 lineages
Fig. 5
Fig. 5
Top 20 significant differentially methylation CpGs between central and effector memory cells ranked by |Δ Beta| with their respective genes in the CD4 and CD8 lineages
Fig. 6
Fig. 6
CD8 TEMRA methylation profiling compared to CD8 central and effector memory cells. a Top 20 significant differentially methylation CpGs in TEMRA versus central and TEMRA versus effector memory comparisons ranked by |Δ Beta| with their respective genes. b 12 shared differentially methylated loci between TEMRA versus central and TEMRA versus effector memory comparisons with their respective genes
Fig. 7
Fig. 7
Heatmap of the methylation profile of the BCL11B gene, demonstrating unique methylation patterns in substantial regions in BCL11B for TEMRA compared to other cell types
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