| dc.description.abstract | Metabolism underpins many processes in cellular biology. Many diseases including cancer often involve aberrant metabolic pathways with altered reliance on metabolites, metabolic enzymes, or metabolic regulators. B lymphocytes are a good model for studying metabolism because they have multiple differentiation states with dynamic energy and biosynthetic requirements. Metabolic sensor and orchestrator of a plethora of metabolic programs, AMP-activated protein kinase (AMPK), is critical for metabolic adaptation to stressful nutrient-limiting conditions in multiple cell types and settings. In my thesis work, I show that AMPK is critical for maintaining the memory B cell population by promoting mitochondria homeostasis. Specifically, AMPK supports mitophagy and mitigates mitochondria-derived reactive oxygen species and lipid peroxidation in memory B cells. In the antibody-secreting cell population, AMPK fine-tunes immunoglobulin synthesis through regulation of mTORC1. AMPK has been shown to influence both glutamine and glucose metabolism, both critical fuels for B cell activation, differentiation, and antibody synthesis. In my thesis work, I show that glucose import and glutamine metabolism synergistically influence antibody production. Understanding critical metabolic pathways of the B lineage may lead to therapeutic targets for effective vaccine development and immune pathologies. | |
