Paradox Found: Global Accounting of Lymphocyte Protein Synthesis

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 lymphocytesin vitroandin vivoelongate at typical rates for mammalian cells. Intriguingly, elongation rates can be increased up to 30% by activationin vivoor fever temperaturein vitro. Resting and activated lymphocytes possess abundant monosome populations, most of which actively translatein vivo,whilein 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 rapidin vivodivision, suggesting that the activated lymphocyte proteomein vivomay 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.