AMPKα1 in B cells promotes memory B cell longevity and mitochondrial homeostasis while dampening antibody synthesis

Abstract

Abstract Emerging evidence indicates that metabolic programs regulate B cell activation and antibody responses. However, the metabolic mediators that support the durability of the memory B cell and long-lived plasma cell populations are not fully elucidated. Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved serine/threonine kinase that integrates cellular energy status and nutrient availability to intracellular signaling and metabolic pathways. Here, we use genetic mouse models to show that B cell restricted loss of the catalytic subunit, AMPKα1, leads to a defect in the long-term survival of the memory B cell population. AMPKα1-deficient memory B lymphocytes exhibited aberrant mitochondrial activity including impaired mitophagy and decreased mitochondrial spare respiratory capacity. In contrast, AMPKα1 was dispensable for the stability of the bone marrow-resident long-lived plasma cell population yet its absence led to increased rates of Ig synthesis and elevated serum antibody concentrations elicited by immunization. Collectively, our findings fit a model in which AMPKα1 supports longevity in the memory B cell compartment by promoting mitochondrial homeostasis but restrains rates of immunoglobulin production by plasma cells.