Interleukin-6 is antiproliferative to a mouse hybridoma cell line and promotive for its antibody productivity

Abstract

Monoclonal antibody production by hybridoma cells at moderately slowed growth states would be favorable for commercial scale production since cells can devote their resources to performing the differentiated function, immunoglobulin production. We found that a purified recombinant human interleukin-6, which had been reported to support or stimulate proliferation of B cell hybridoma/plasmacytoma cells, suppressed growth of a hybridoma cell line in serum-free medium. In the presence of the interleukin, the growth-suppressed cells were viable for remarkably long periods in batch culture, and after removal of the interleukin from the culture medium, they started to proliferate at their normal growth rate. As the concentration of the interleukin increased in the culture, the growth rate decreased and the specific antibody productivity (antibody production rate per cell) increased to 5-fold of control at 10 U ml-1 (2 ng ml-1) of the interleukin.

Differential macrophage modulation of asymmetric IgG antibody synthesis by soluble or particulate stimuli

“…It is known that IL-6 has an antiproliferative effect on several murine hybridomas [39]. Our results showed an inhibitory effect of the CSPM from OVA-polystyrene-stimulated macrophages on the proliferation of the hybridoma 112D5, indicating that the increase in the levels of asymmetric IgG cannot be attributed to a greater proliferation rate of the cells but to an increase synthesis of this antibody.…”

Growth control of hybridoma cells with an artificially induced EpoR-gp130 heterodimer

“…Today, MAbs are predominantly produced by hybridoma cell culture, which needs to be supplemented with cytokines and growth factors for controlling cell growth (Doverskog et al 1997). One of the key cytokines is IL-6, which was originally identified as B-cell stimulatory factor-2 and was shown to affect hybridoma growth and also stimulate antibody productivity (Makishima et al 1992). In the proposed mechanism, IL-6 binds to IL-6R and gp130 (Bravo et al 1998;Hibi et al 1990;Muller-Newen et al 2000) to form hexameric complex composed of two molecules of each component (Paonessa et al 1995;Skiniotis et al 2005;Ward et al 1996).…”

Replacing factor‐dependency with that for lysozyme: Affordable culture of IL‐6‐dependent hybridoma by transfecting artificial cell surface receptor

“…In contrast, IL-6 has also been reported to inhibit hybridoma growth in serum-free medium. This can lead to an increase in antibody production in prolonged culture by keeping cells viable and preventing cell overgrowth after the cell number reached optimal levels (Makishima et al, 1992).…”

“…IL-6 was originally identified as B-cell stimulatory factor-2 and was shown to affect hybridoma growth and antibody productivity (Makishima et al, 1992). In the proposed mechanism, IL-6 binds to IL-6R and gp130 (Bravo et al, 1998;Hibi et al, 1990;Muller-Newen et al, 2000) to form a hexameric complex composed of two molecules of each component (Paonessa et al, 1995;Ward et al, 1996).…”