School of Medicine
Microbiology, Immunology, and Cell Biology
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.
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