Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function

Authors

Wing Y. Lam, Washington University School of Medicine
Arijita Jash, Washington University School of Medicine
Cong-Hui Yao, Washington University
Lucas D'Souza, University of Arizona
Rachel Wong, University of Arizona
Ryan M. Nunley, Washington University Orthopedics
Gordon P. Meares, West Virginia University
Gary J. Patti, Washington University
Deepta Bhattacharya, University of ArizonaFollow

Author ORCID Identifier

N/A

N/A

N/A

https://orcid.org/0000-0003-4132-7328

N/A

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https://orcid.org/0000-0002-0805-0155

N/A

N/A

https://orcid.org/0000-0001-8377-7699

Document Type

Article

Publication Date

2018

College/Unit

School of Medicine

Department/Program/Center

Microbiology, Immunology, and Cell Biology

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 life- spans. Long-lived plasma cells imported more fluo- rescent 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 re- ductions in both antibody secretion and mitochon- drial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respira- tion and anaplerotic reactions, yielding glutamate and aspartate for antibody synthesis. Endoplasmic reticulum (ER) stress responses, which link meta- bolism to transcriptional outcomes, were similar between long- and short-lived subsets. Accordingly, population and single-cell transcriptional compari- sons across mouse and human plasma cell subsets revealed few consistent and conserved dif- ferences. Thus, plasma cell antibody secretion and lifespan are primarily defined by non-transcriptional metabolic traits.

Digital Commons Citation

Lam, Wing Y.; Jash, Arijita; Yao, Cong-Hui; D'Souza, Lucas; Wong, Rachel; Nunley, Ryan M.; Meares, Gordon P.; Patti, Gary J.; and Bhattacharya, Deepta, "Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function" (2018). Faculty & Staff Scholarship. 1407.
https://researchrepository.wvu.edu/faculty_publications/1407

Source Citation

Lam, W. Y., Jash, A., Yao, C.-H., D’Souza, L., Wong, R., Nunley, R. M., Meares, G. P., Patti, G. J., & Bhattacharya, D. (2018). Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function. Cell Reports, 24(9), 2479–2492.e6. https://doi.org/10.1016/j.celrep.2018.07.084