Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function
AuthorLam, Wing Y.
Nunley, Ryan M.
Meares, Gordon P.
Patti, Gary J.
AffiliationUniv Arizona, Coll Med, Dept Immunobiol
MetadataShow full item record
CitationWing Y. Lam, Arijita Jash, Cong-Hui Yao, Lucas D’Souza, Rachel Wong, Ryan M. Nunley, Gordon P. Meares, Gary J. Patti, Deepta Bhattacharya, Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function, Cell Reports, Volume 24, Issue 9, 2018, Pages 2479-2492.e6, https://doi.org/10.1016/j.celrep.2018.07.084.
Rights© 2018 The Author(s).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractPlasma 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.
NoteOpen access journal.
VersionFinal published version
SponsorsNIH [R01AI099108, R01AI129945, R01ES022181, R01NS099304]; New York Stem Cell Foundation; National Science Foundation [DGE-1143954]; NCI Cancer Center Support Grant [P30 CA91842]; ICTS/CTSA from the National Center for Research Resources (NCRR), a component of the NIH [UL1TR000448]; NIH Roadmap for Medical Research
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