Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells

Abstract Memory B cells (MBCs) are long-lived and produce high-affinity, generally, class-switched antibodies. Here we use a multiparameter approach involving CD27 to segregate naïve (NBCs), IgD+ unswitched (unsw) MBCs IgG+ or IgA+ (sw) from humans of different age, sex race. Conserved antibody variable gene expression indicates that emerge through unbiased selection NBCs. Integrative analyses mRNAs, miRNAs, lncRNAs, chromatin accessibility cis-regulatory elements uncover core mRNA-ncRNA transcriptional signature shared by swMBCs distinct NBCs, while unswMBCs display transitional transcriptome. Some swMBC loci accessible but not expressed in Profiling miRNAs reveals downregulated MIR181 concomitantly upregulated target-genes RASSF6, TOX, TRERF1, TRPV3 RORa swMBCs. Finally, lncRNAs differentially cluster proximal chromosome 14 IgH chain locus. Our findings provide new insights into MBC programs epigenetic regulation, opening investigative avenues on these critical cell human health disease.