Oral Presentation 45th Lorne Genome Conference 2024

Unravelling the hierarchical chromatin Landscape of Immune Memory Cells (#33)

Hannah D Coughlan 1 2 , Timothy M Johanson 1 2 , Sara Berent 1 2 , Lizhong Chen 1 2 , Brigette C Duckworth 1 2 , Ben J Broomfield 1 2 , Carolina Alvarado 1 2 , George W Ashdown 1 2 , Sam WZ Olechnowicz 1 2 , Peter F Hickey 1 2 , Michael J Mlodzianoski 1 2 , Kelly L Rogers 1 2 , Joanna R Groom 1 2 , Alexandra L Garnham 1 2 , Rhys Allan 1 2 , Gordon Smyth 1 3
  1. Walter and eliza hall institute of medical research, Parkville, VIC, Australia
  2. Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
  3. School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia

We employed a bioinformatic-driven approach, integrating HiC, ATAC-seq and RNA-seq, to unravel the intricate hierarchical chromatin landscape of memory immune cells. We studied key components of the adaptive immune system: memory B and T cells. Adaptive immune memory is a specialized mechanism where immune cells "remember" previous encounters with pathogens, allowing for a quicker and more effective response upon re-exposure. Little is known about the epigenetics of memory immune cells especially compared to their naïve counterparts. Through differential analysis it appears that modules of differentially expressed genes and components of chromatin structure are shared between memory T and B cells while others are unique to a cell type.

From HiC data, our investigation delves into the unique and memory specific long-range chromatin structure of B cells compared to T cells. Intriguingly, through imaging, we uncover that memory B cells also possess uniquely decondensed chromatin.

Through statistically robust differential analysis of DNA accessibility and HiC data, we observe that the genome of B cells undergoes fewer changes upon memory formation compared to T cells. B cells are generally more accessible however we find shared regions that increase in accessibility with memory formation. This indicates there is a memory epigenetic state independent of cell type.  

Additionally, we explored the activation dynamics of naïve and memory B cells. Our research sheds light on the convergence of transcriptional and epigenetic profiles in naïve and memory B cells upon activation. This convergence underscores the intricate regulatory mechanisms at play during immune memory development.

Our multi-omic analysis, not only unveils the hierarchical chromatin landscape governing immune memory cells but also offers insights into the differential epigenetic and transcriptional regulation within B and T cells. These discoveries have profound implications for our understanding of immune memory and its impact on long-term immunity, vaccine responses, and immunotherapies.