Washington University in St. Louis

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Metabolomics to elucidate novel biochemical mechanisms of disease
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Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function

Lam WY, Jash A, Yao C-H, D'Souza L, Wong R, Nunley RM, Meares GP, Patti GJ, and Bhattacharya D
Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function
Cell Reports, 24, 2479-2492, 2018
doi:10.1016/j.celrep.2018.07.084

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.

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