Synthesis and regulation of trans-mRNA encoding the immunoglobulin epsilon heavy chain.

We have detected an immunoglobulin heavy-chain trans-mRNA of the epsilon class in which the variable region of the human transgenic mu chain is correctly spliced to the first exon of the endogenous mouse epsilon constant region. Together with our previous observations, all the endogenous isotypes that are targets of class switching have proved to be expressed as trans-mRNA. This indicates that immunoglobulin trans-mRNA synthesis is a general mechanism to express a second heavy-chain isotype with the variable region of the transgenic mu chain. Synthesis of epsilon trans-mRNA is regulated in a way similar to the trans-mRNAs of the gamma subclasses or class switching to epsilon, i.e., interleukin-4 can induce the germline transcript of the epsilon constant region, but costimulation with lipopolysaccharide is necessary for epsilon trans-mRNA expression. The amount of epsilon trans-mRNA induced is similar to that of gamma 1 and higher than expected as judged from the rate of class switching to epsilon. All these data are consistent with our previous hypothesis that trans-mRNA is synthesized by a trans-splicing mechanism and that this mechanism is involved in the simultaneous multiple-isotype expression of immunoglobulin in a single B lymphocyte.