@article{88416838f8004c5492e02918a57e1978,
title = "Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function",
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.",
keywords = "cell respiration, endoplasmic reticulum stress, glucose metabolism, glutamine metabolism, glycosylation, hexosamine biosynthesis, immunoglobulin biosynthesis, plasma cells, single-cell RNA-sequencing",
author = "Lam, {Wing Y.} and Arijita Jash and Yao, {Cong Hui} and Lucas D'Souza and Rachel Wong and Nunley, {Ryan M.} and Meares, {Gordon P.} and Patti, {Gary J.} and Deepta Bhattacharya",
note = "Funding Information: This work was supported by NIH grants R01AI099108 and R01AI129945 (to D.B.), R01ES022181 (to G.J.P.), and R01NS099304 (to G.P.M.). This work was also supported by a Robertson Investigator award from The New York Stem Cell Foundation (to D.B.). R.W. was supported by a predoctoral fellowship from the National Science Foundation (DGE-1143954). We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant UL1TR000448 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Funding Information: This work was supported by NIH grants R01AI099108 and R01AI129945 (to D.B.), R01ES022181 (to G.J.P.), and R01NS099304 (to G.P.M.). This work was also supported by a Robertson Investigator award from The New York Stem Cell Foundation (to D.B.). R.W. was supported by a predoctoral fellowship from the National Science Foundation ( DGE-1143954 ). We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant UL1TR000448 from the National Center for Research Resources (NCRR) , a component of the NIH , and NIH Roadmap for Medical Research . This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = aug,
day = "28",
doi = "10.1016/j.celrep.2018.07.084",
language = "English (US)",
volume = "24",
pages = "2479--2492.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}