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

0892-6638/93/0007-0149/$01.50. © FASEB 149 ABSTRACT We have detected an immunoglobulin heavy-chain trans-mRNA of the e class in which the variable region of the human transgenic t chain is correctly spliced to the first exon of the endogenous mouse #{128} 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 i chain. Synthesis of #{128} trans-mRNA is regulated in a way similar to the trans-mRNAs of the ‘y subclasses or class switching to e, i.e., interleukin-4 can induce the germline transcript of the #{128}constant region, but costimulation with lipopolysaccharide is necessary for #{128} trans-mRNA expression. The amount of #{128} trans-mRNA induced is similar to that of yl and higher than expected as judged from the rate of class switching to #{128}.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 multipleisotype expression of immunoglobulin in a single B lymphocyte. Shimizu, A., Honjo, T. Synthesis and regulation of trans-mRNA encoding the immunoglobulin e heavy chain. FASEBJ. 7: 149-154; 1993.