Optimisation of the Fatty Acid Composition of a Hybridoma Enhances Mab Production and Perturbs Energy Metabolism

Abstract

Unsaturated fatty acids stimulate growth and antibody productivity of serum-free hybridoma cultures. However continuous culture passage with fatty acids results in a gradual decline in Mab productivity. The inability of cells to regulate uptake results in the accumulation of exogenous fatty acids in all cellular lipid fractions. The saturated/ unsaturated fatty ratio of the polar lipid fraction changed from 1.39 to 0.13 following one culture passage with linoleic acid.

The increased linoleic composition of polar lipids is associated with a decreased permeability of membranes for glutamine. Consequently the cells rely increasingly on glucose for energy metabolism. This results in a significant increase in the specific lactate production rate and the molar yield coefficient, Y_lac/glc The metabolic changes are reversed by growing the cells in fatty acid-free media. This also restores the cells to high Mab productivity. The optimal intracellular lipid content is finely balanced between a reduced and over-loaded state. The fatty acid composition of the cells has been analysed at the point of maximum Mab productivity.