A central function of the adaptive immune system is to ‘remember’ encounters with pathogens, or other threats, and respond more rapidly and effectively to subsequent encounters. This is the key process induced, or (less charitably) exploited, by vaccination.
Despite their importance, immune memory cells and the molecular processes that underpin their formation are incompletely understood. To explore memory formation more fully, we generated and integrated matched three-dimensional genome architecture (in situ HiC), chromatin accessibility (ATAC-Seq) and transcriptomic (RNA-Seq) data to reveal the multi-dimensional molecular changes underlying the formation of the two arms of adaptive murine memory (T and B cells). We performed similar analyses of activated naïve and memory B cells over time to explore the molecular ‘advantages’ of memory B cells over their naïve counterparts.
While unorthodox, the comparison of naïve and memory T and B cells from the same mice revealed: unexpected common molecular changes across all memory cell transitions, differential utilisation of common gene regulatory mechanisms by T and B cells, genome architectural residues of activation preserved uniquely in memory B cells, among others.
In addition to being a valuable molecular characterisation and resource of immune memory, our data provide targets for both total adaptive immune memory modification and lineage-specific targeting, potentially exploitable in future vaccine optimisation and design.