Epigenetic priming in memory B cells versus naive B cells results in differential induction genes related to T-B interactions 3391

Abstract Description Naïve B cells (NBCs) and memory B cell (MBC) subsets can be distinguished by unique epigenetic states, which often results in meaningful gene expression in the resting cells. However, these cells also differ in genes that are readily accessible yet lack substantive expression, i.e., gene priming. To test whether differential priming of genes in NBCs and MBCs results in differential gene induction, we stimulated these cells via BCR, CD40, IL-21, and combinations thereof, culminating in nearly 200 bulk RNA-seq samples. Many primed genes in MBCs were more rapidly and strongly induced compared to NBCs in response to the stimuli tested. Interestingly, some of these genes are implicated in T-B interactions; the chemokines and cytokines Cx3cr1, Cxcl16, Il1b, IL6. Il10, and Ccl22 (a potent recruiter of Tregs and TFH), and the surface proteins Tnfsf9 and Ly75. Often, the most PC-prone MBCs typically displayed the highest induction compared to NBCs upon stimulation, whereas GC-prone MBCs were less induced. Yet in cases such as Il1b and Il6, GC-prone MBCs displayed a higher induction. Interestingly, PC-prone MBCs, especially those originating from a GC, uniquely induced genes such as Cd70, Tnfrsf8, and Il33. Our findings provide novel insight into the epigenetic mechanisms of MBC activation and differentiation and suggests NBCs and MBCs may have qualitatively different interactions with T cells, which could lead to interventions specific to a primary versus secondary response. Funding Sources Immunology of Infectious Disease T32 (AI060525) R01 AI043603 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)