Population balance between producing and nonproducing hybridoma clones is very sensitive to serum level, state of inoculum, and medium composition.

Secreting and nonsecreting hybridoma populations derived from the murine hybridoma cell line 167.4G5.3 were each grown in batch culture in low serum and serum-free media. Under serum-free conditions, a secreting population gained on a predominantly nonsecreting population and competed with the existing antibody-deficient cells effectively. It was found that this competition was sensitive to state of inoculum and medium composition. We conclude that the competition between a secreting and nonsecreting, or more generally, a producing and nonproducing, population is important; the appearance of the latter may not be a significant setback in terms of expected product titer.