Antibody Productivity of CHO Cells is Altered by ER Stress Tolerance of the Host Cell

We compared high- and low-producing Chinese hamster ovary (CHO) cell clones of two types of antibodies to explore the factors involved in the antibody productivity. A comparison of antibody gene copy numbers showed that, as expected, more genes were introduced in the genomes of the high-producing clones than in the genomes of the low-producing clones. However, specific productivity (Qp) was not in a direct proportional relationship to gene copy numbers and the quantities of mRNAs. The Qp values were lower than the values expected by the increase of genes or mRNAs, which may have been due to the limited rates of transcription and translation. Further comparisons were performed by proteome analyses. The results showed that endoplasmic reticulum (ER) stress occurred in the low-producing clones, resulting in apoptosis. The expression of genes related to the TCA cycle was decreased in cells with low viable cell density (VCD), even in high-producing clones. These results indicate that CHO host cells are diverse, with some cells tolerant to ER stress and others less tolerant. For less tolerant cells, ER stress is induced by antibody production, and their viability is reduced by apoptosis. Consequently, only clones with low copy numbers and low production were produced. On the other hand, the ER stress-tolerant cells yielded high-producing clones with high copy numbers. However, VCD is thought to decrease as Qp increases. These results indicate that suppression of ER stress associated with high antibody production is important for antibody production by CHO cells.