We have shown that one of the alleles in a hybridoma was nonproductive because the sequence in the N region of the heavy chain caused it to be out of frame and to terminate prematurely. This allele became productive, and the γ1 heavy chain that it encoded was secreted when an adenosine was inserted to produce an open reading frame. This event occurred at a very low frequency following mutagenesis of the cultured cells. This result suggests that similar sorts of events must occur in vivo when both productive and nonproductive alleles undergo frequent mutations and that new genes may be expressed in hybridomas as they are being subcloned.
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