title: Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells.
abstract: 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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Wing Y
authors.initials: WY
authors.lastname: Lam
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Becker
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Krista M
authors.initials: KM
authors.lastname: Kennerly
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Curtis
authors.affiliation: Department of Chemistry, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Llufrio
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Kyle S
authors.initials: KS
authors.lastname: McCommis
authors.affiliation: West Coast Metabolomics Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Johannes
authors.initials: J
authors.lastname: Fahrmann
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Pizzato
authors.affiliation: Washington University Orthopedics, Barnes Jewish Hospital, Saint Louis, MO 63110, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Nunley
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wolfgang
authors.affiliation: Department of Chemistry, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Patti
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Brian N
authors.initials: BN
authors.lastname: Finck
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Pearce
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: deeptab@wustl.edu.
authors.forename: Deepta
authors.initials: D
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D001693:Biological Transport, Active; D019069:Cell Respiration; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology*; D045706:Proprotein Convertase 2 / Q000235:genetics / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D013312:Stress, Physiological / Q000276:immunology
chemical_list: D007136:Immunoglobulins; D019289:Pyruvic Acid; C473668:Pcsk2 protein, mouse; D045706:Proprotein Convertase 2; D005947:Glucose