Are human memory B cells ‘poised’ to become plasma cells? 4156

Abstract Description During a recall immune response, memory B cells differentiate into plasma cells (PCs), which are indispensable for antibody production and humoral immunity. Furthermore, memory B cells proliferate sooner and require less stimulation to differentiate into PCs relative to naïve B cells and can thus be considered ‘poised’. The exact mechanisms explaining this discrepancy remain incompletely understood. Our lab has previously observed that mouse Marginal Zone (MZ) B cells are analogously ‘poised’ to become PCs relative to Follicular (FO) B cells. Transcriptomic analyses have shown that MZ B cells are enriched for hallmark mTORC1 signaling, unfolded protein response (UPR) pathway, and Myc target gene signatures compared to FO B cells, which are all required for PC differentiation. We hypothesized that these same gene signatures would be enriched in human memory B cells. From a cohort of healthy human donors, RNA-sequencing was performed on splenocytes. Indeed, we observe these same hallmark gene signatures enriched in memory B cells along with others involved in the synthesis of ribosomal proteins and translation. These results suggest that human memory B cells are better equipped to produce massive amounts of proteins that involve mTORC1 and Myc activity along with the UPR pathway, all of which are needed for antibody production by PCs. The better we understand PC differentiation mechanisms, the higher potential they can be manipulated for clinically relevant purposes. Funding Sources 5RO1AI175185-02 - Biochemical Mechanisms for Sustained Humoral Immunity Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)