Washington University in St. Louis

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Metabolomics to elucidate novel biochemical mechanisms of disease
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Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells

Lam WY, Becker AM, Kennerly KM, Wong R, Curtis JD, Llufrio EM, McCommis KS, Fahrmann J, Pizzato HA, Nunley RM, Lee J, Wolfgang MJ, Patti GJ, Finck BN, Pearce EL, Bhattacharya D
Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells
Immunity, 45(1), 60-73, 2016
doi:10.1016/j.immuni.2016.06.011

Durable antibody production after vaccination or infection is mediated by long-lived plasma cells (LLPCs). Pathways that specifically allow LLPCs to persist remain unknown. Through bioenergetic profiling, we found that human and mouse LLPCs could robustly engage pyruvate-dependent respiration, whereas their short-lived counterparts could not. LLPCs took up more glucose than did short-lived plasma cells (SLPCs) in vivo, and this glucose was essential for the generation of pyruvate. Glucose was primarily used to glycosylate antibodies, but glycolysis could be promoted by stimuli such as low ATP levels and the resultant pyruvate used for respiration by LLPCs. Deletion of Mpc2, which encodes an essential component of the mitochondrial pyruvate carrier, led to a progressive loss of LLPCs and of vaccine-specific antibodies in vivo. Thus, glucose uptake and mitochondrial pyruvate import prevent bioenergetic crises and allow LLPCs to persist. Immunizations that maximize these plasma cell metabolic properties might thus provide enduring antibody-mediated immunity.

Washington University, Departments of Chemistry, Genetics, and Medicine. Saint Louis, Missouri 63110 USA