Paradoxical imbalance between activated lymphocyte protein synthesis capacity and rapid division rate

• Published in: eLife Vol. 12
• Main Authors: Seedhom, Mina O, Dersh, Devin, Holly, Jaroslav, Pavon-Eternod, Mariana, Wei, Jiajie, Angel, Matthew, Shores, Lucas, David, Alexandre, Santos, Jefferson, Hickman, Heather, Yewdell, Jonathan W
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 21.03.2024; eLife Sciences Publications Ltd; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Amino acids; Animals; B cells; Cell activation; Cell Biology; Cell division; Cellular proteins; Cytokines; Experiments; Flow Cytometry; Genetic translation; Immunology and Inflammation; Life Sciences; Lymphocytes; Mammalian cells; Mammals; Metabolism; Methods; Mice; OT-I; Protein Biosynthesis; Protein synthesis; Proteins; Proteomes; Ribonucleic acid; ribopuromycylation; Ribosomes; Ribosomes - metabolism; RNA; T cells; Transfer RNA; Translation initiation; Translations; Variance analysis; mouse; ribosomes; cell biology; OT-I; inflammation; ribopuromycylation; T cells; human; immunology
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.89015

Rapid lymphocyte cell division places enormous demands on the protein synthesis machinery. Flow cytometric measurement of puromycylated ribosome-associated nascent chains after treating cells or mice with translation initiation inhibitors reveals that ribosomes in resting lymphocytes in vitro and in vivo elongate at typical rates for mammalian cells. Intriguingly, elongation rates can be increased up to 30% by activation in vivo or fever temperature in vitro. Resting and activated lymphocytes possess abundant monosome populations, most of which actively translate in vivo, while in vitro, nearly all can be stalled prior to activation. Quantitating lymphocyte protein mass and ribosome count reveals a paradoxically high ratio of cellular protein to ribosomes insufficient to support their rapid in vivo division, suggesting that the activated lymphocyte proteome in vivo may be generated in an unusual manner. Our findings demonstrate the importance of a global understanding of protein synthesis in lymphocytes and other rapidly dividing immune cells.