The effect of the rat immunoglobulin heavy-chain 3' enhancer is position dependent.

We tested the effect of the immunoglobulin (Ig) heavy- and kappa-chain 3' enhancers on the expression of Ig genes in B-cells. Inclusion of the heavy-chain 3' enhancer in addition to the mu intron enhancer increased the expression rate up to sixfold, but this effect was strongly position dependent, in that it was only observed when the element was located downstream from the constant exons. Furthermore, the stimulatory effect could be augmented by increasing the distance between the constant gene segments and the 3' enhancer. When the 3' enhancer was located upstream from the variable gene promoter, the transcription was dramatically suppressed. Thus, the heavy-chain 3' enhancer does not fit into the usual definition of an enhancer element. The implications for the production of recombinant antibodies are discussed.