title: Regulated expression of immunoglobulin trans-mRNA consisting of the variable region of a transgenic mu chain and constant regions of endogenous isotypes.
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 mu chain gene. In this study we further investigated regulation of trans-mRNA expression. Regulated expression of different gamma subclasses of trans-mRNA was similar to that of class switching: IL-4 together with lipopolysaccharide (LPS) predominantly increased the amount of gamma 1 trans-mRNA whereas LPS alone mainly induced gamma 3 and gamma 2b trans-mRNAs. Expression of the gamma 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-beta induced germline transcripts of the alpha chain CH gene but had no obvious effects on alpha trans-mRNA induction. Both C alpha 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-C mu 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 mu chain transgenes.
authors.affiliation: Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Honjo
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001483:Base Sequence; D004274:DNA, Recombinant; D005786:Gene Expression Regulation / Q000187:drug effects; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D004274:DNA, Recombinant; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D015847:Interleukin-4