Regulated expression of immunoglobulin trans-mRNA consisting of the variable region of a transgenic μ chain and constant regions of endogenous isotypes

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Abstract
Our previous work demonstrated that chimeric immunoglobulin mRNAs (trans-mRNAs) composed of a transgenic VHDJH region and endogenous CH sequences could be synthesized, most likely by a trans-splicing mechanism, in a transgenic line carrying a rearranged human membrane-type μ chain gene. In this study we further investigated regulation of trans-mRNA expression. Regulated expression of different γ subclasses of trans-mRNA was similar to that of class switching: IL-4 together with lipopolysaccharide (LPS) predominantly increased the amount of γ1trans-mRNA whereas LPS alone mainly induced γ3 and γ2b trans-mRNAs. Expression of the γ class trans-mRNAs was preceded by germline transcription from the corresponding CH genes, but the co-existence of such germline transcripts and transgene transcripts was not sufficient for trans-mRNA production. Transforming growth factor-β induced germline transcripts of the a α chain CH gene but had no obvious effects on α trans-mRNA induction. Both Cα gene alleles were used in trans-mRNA but in different frequencies. We could also detect trans-mRNA expression in another transgenic mouse line which carries a rearranged mouse VHDJH-Cμ gene. These results indicate that trans-mRNA synthesis is not restricted to either a particular transgenic line or an isotype, but is a general mechanism to express a second isotype with the VH regions of rearranged n chain transgenes.

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