Loss of antibody productivity is highly reproducible in multiple hybridoma subclones

An immunoglobulin G (IgG 2b ) producing hybridoma cell line (S3H5/γ2bA2) was cloned and subcloned. Twenty subclones were grown in parallel while being adapted in a stepwise fashion to serum‐free medium. Following adaptation to serum‐free medium, it was found that 16 of the 20 subclones remained at a relatively constant proportion of nonproducing cells. Three of the remaining subclones transiently deviated from this balance but eventually returned toward this population composition. One subclone continued to lose productivity. A population balance was reached at approximately 8% of the population being nonproducers. The loss of antibody productivity was thus highly reproducible. © 1993 John Wiley & Sons, Inc.