CELL-CYCLE KINETICS AND MONOCLONAL-ANTIBODY PRODUCTIVITY OF HYBRIDOMACELLS DURING PERFUSION CULTURE

The flow-cytometric (FCM) analysis of bivariate DNA/IgG distributions has been conducted to study the cell cycle kinetics and monoclonal ant ibody (MAb) production during perfusion culture of hybridoma cells. Th ree different perfusion rates were employed to demonstrate the depende ncy of MAb synthesis and secretion on cell cycle and growth rate. The results showed that, during the rapid growth period of perfusion cultu re, the level of intracellular IgG contents of hybridoma cells changed significantly at each perfusion rate, while the DNA histograms showin g cell cycle phases were almost constant. Meanwhile, during the reduce d growth period of perfusion culture, the fraction of cells in the S p hase decreased, and the fraction of cells in the G1/G0 phase increased with decreasing growth rate. The fraction of cells in the G2/M phase was relatively constant during the whole period of perfusion culture. Positive correlation was found between mean intracellular IgG contents and the specific MAb production rate, suggesting that the deletion of intracellular IgG contents by a flow cytometer could be used as a goo d indicator for the prediction of changes in specific MAb productivity following manipulation of the culture condition. (C) 1994 John Wiley & Sons, Inc.