ESSENTIAL ROLE OF OPTIMAL PROTEIN-SYNTHESIS IN PREVENTING THE APOPTOTIC DEATH OF CULTURED B-CELL HYBRIDOMAS

The monoclonal antibody productivity of cell culture systems is strong ly dependent on the maintenance of hybridoma cell viability. We report that partial (< 50%) and transient (3 h) inhibition of protein synthe sis by cycloheximide or deprivation of an essential amino acid induces apoptosis (programmed cell death) in B cell hybridomas. This unusual mechanism of apoptosis induction is likely to play a significant role in limiting cell viability in batch and perfusion cultures of hybridom as and emphasizes the importance of constantly maintaining a near opti mal rate of macromolecular synthesis by optimization of all culture pa rameters. Inhibition of apoptosis in hybridomas by cell engineering an d other technologies should permit, in the near future, a significant increase in the antibody productivity of existing cell culture systems .