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Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying lifespans. Long-lived plasma cells imported more fluorescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered reductions in both antibody secretion and mitochondrial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respiration and anaplerotic reactions, yielding glutamate and aspartate for antibody synthesis. Endoplasmic reticulum (ER) stress responses, which link metabolism to transcriptional outcomes, were similar between long- and short-lived subsets. Accordingly, population and single-cell transcriptional comparisons across mouse and human plasma cell subsets revealed few consistent and conserved differences. Thus, plasma cell antibody secretion and lifespan are primarily defined by non-transcriptional metabolic traits., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy. Many of these processes are likely to be linked, thereby affording possibilities to improve vaccine design and to develop new therapies for autoimmunity. We review here aspects of plasma cell biology with an emphasis on recent studies and the relationships between intermediary metabolism, antibody production, and lifespan., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)