The enhancement of human monoclonal antibody production by retinoic acid (RA) was evaluated using the human-human hybridoma cell line BD9 under serum-free culture condition. The amount of human IgG secreted by BD9 hybriodmas was enhanced about eight-fold by treatment with 10-7 M of RA for 4 days. Northern blot analysis showed that both mRNA levels of the IgG light and heavy chains were markedly increased by RA when compared with control without RA treatment. On the other hand, it was found that continuous treatment of cells with RA was not always required to exhibit the enhancing effect, suggesting that RA may act as a trigger for IgG gene expression. The comparison between extra- and intracellular IgG amounts by immunoblot analysis suggests that the secretion rate of IgG may be accelerated by RA treatment. These results suggest that RA may be an effective culture additive for efficient production of human monoclonal antibody using human-human hybridomas.
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