Immunometabolic effects of lactate on B cell function in healthy individuals of different ages

Abstract

AbstractAging is characterized by chronic systemic inflammation and metabolic changes. When we compared B cells from young and elderly donors, we found that aging induces higher oxygen consumption rates, and especially higher extracellular acidification rates, measures of oxidative phosphorylation and of anaerobic glycolysis, respectively. Importantly, this higher metabolic status, which reflects the age-associated expansion of pro-inflammatory B cell subsets, was found associated with higher secretion of lactate and autoimmune antibodies after in vitro stimulation. B cells from elderly individuals, induce in vitro generation of pro-inflammatory CD4+ T cells from young individuals through metabolic pathways mediated by lactate secretion. Lactate also induces immunosenescent B cells that are glycolytic and express transcripts for multiple pro-inflammatory molecules. These results altogether may have relevant clinical implications and suggest novel targets for therapeutic interventions in patients with inflammatory conditions and diseases.