Regulation of glucose and glutamine uptake and the production of monoclonal antibody in hybridoma cultures

Abstract

The relationship between the uptake of glucose and glutamine and the partitioning of these substrates into hybridoma growth and monoclonal antibody production at steady state in a chemostat was investigated. The mouse-mouse hybridoma cell line 6BB which produces IgM against human blood group B was used. It was observed that the specific uptake rate of the rate-limiting substrate (Q(s)) was determined by the residual concentration of the substrate in the culture (R(s)); however, the specific growth rate of the culture was not strictly determined by R(s) as described by the Monod Relation nor determined by Q(s). The specific rate of production of monoclonal antibody (Q(ub)) was a function of dilution rate and the concentration of the rate-limiting substrate in the medium reservoir. Simple mathematical models were developed which suggested that the rate-limiting substrate taken up by the cultures was channeled either into biomass or antibody production. Partitioning of the rate-limiting substrate was a result of competition between the cell growth and the antibody production mechanism.