Cell‐cycle‐dependent protein accumulation by producer and nonproducer murine hybridoma cell lines: A population analysis

Sandra J. Kromenaker, Friedrich Srienc

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Single‐cell rates of accumulation of cellular protein have been determined as a function of total protein content using flow cytometry and population balance equations for exponentially growing murine hybridoma cells in the individual G1, S1 and G2 + M cell cycle phases. A novel flow cytometric technique for the identification of hybridoma cells in mitosis was developed and implemented. The data were obtained from a producer cell line which synthesizes and secretes high levels of monoclonal antibodies, and from a nonproducer clone which does not synthesize and secrete substantial amounts of antibody. The results indicate that the kinetics of single‐cell protein accumulation in these two cell lines are considerably different. In particular, low protein content G1 phase producer cells were characterized by a rate of protein accumulation which was approximately five times higher than the mean rate observed for higher protein content producer cells cycle phase. In contrast, the rate of accumulation of protein increased continuously with totalprotein content for the G1 phase nonproducer cells. S phase hybridoma cells were characterized by a considerably lower rate of protein accumulation which did not vary much with protein content for either cell line. Finally, G2 + M phase producer cells demonstrated a negative rate of protein accumulation which indicates that the rates of protein synthesis. It was hypothesized that these differences in total protein accumulation are caused by differences in monoclonal antibody accumulation. The distribution of rates suggests the need for a segregated approach to the modeling of the kinetics of antibody production in hybridomas.

Original languageEnglish (US)
Pages (from-to)665-677
Number of pages13
JournalBiotechnology and bioengineering
Issue number6
StatePublished - Sep 1991


  • cell cycle
  • flow cytometry
  • hybridoma
  • population balance

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