Naïve T and B lymphocytes undergo extensive metabolic changes during their differentiation to effector and memory cells, which clear the invading pathogens during primary response and provide long-term immunity upon secondary exposures. Though naïve T and B cells are in a state of metabolic quiescence, upon exposure to their cognate antigens, they rapidly alter their metabolic outputs to acquire distinct metabolic states associated with effector and memory phenotypes. During the acute phases of clonal expansion and effector differentiation, adaptive immune cells are engaged in anabolic processes and rely on aerobic glycolysis as the primary source of energy. Whereas, during memory differentiation, adaptive immune cells switch to catabolic programs which largely rely on mitochondrial oxidative phosphorylation to augment survival in a nutrient scarce environment. Our recent studies have shown how modulation of cellular metabolism by alterations in mitochondrial dynamics could influence generation of long-term immunological memory and effective immune responses (BioRxiv, 2022). Interestingly, several epigenetic modulators including TET enzymes depend of cellular metabolites as co-factors for their activity. We are interested in understanding how changes in the metabolic outputs, that are associated with distinct stages of B (and T) cell differentiation impacts their epigenetic landscapes. We aim to uncover these mechanisms with the objective to design approaches to engineer the desired epigenetic states in immune cells that could in turn enhance the fidelity of immune responses.