Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function

Wing Y. Lam, Arijita Jash, Cong Hui Yao, Lucas D'Souza, Rachel Wong, Ryan M. Nunley, Gordon P. Meares, Gary J. Patti, Deepta Bhattacharya

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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. Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Lam et al. demonstrate that short- and long-lived plasma cells are distinguished by metabolic properties such as nutrient uptake. In contrast, very few conserved transcriptional changes are observed between plasma cells of varying longevity.

Original languageEnglish (US)
Pages (from-to)2479-2492.e6
JournalCell Reports
Volume24
Issue number9
DOIs
StatePublished - Aug 28 2018

Keywords

  • cell respiration
  • endoplasmic reticulum stress
  • glucose metabolism
  • glutamine metabolism
  • glycosylation
  • hexosamine biosynthesis
  • immunoglobulin biosynthesis
  • plasma cells
  • single-cell RNA-sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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