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 strongly dependent on the maintenance of hybridoma cell viability. We report that partial (< 50%) and transient (3 h) inhibition of protein synthesis 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 hybridomas and emphasizes the importance of constantly maintaining a near optimal rate of macromolecular synthesis by optimization of all culture parameters. Inhibition of apoptosis in hybridomas by cell engineering and other technologies should permit, in the near future, a significant increase in the antibody productivity of existing cell culture systems.
Perreault
J
J
Canadian Red Cross, Blood Services, Terminus, Québec.
Lemieux
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D006825:Hybridomas / Q000166:cytology* / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors