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PMID: 1903429 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene.

The Journal of experimental medicine ·Vol. 173 ·No. 6 ·1991-06-01 ·Pages 1385-93

Shimizu A, Nussenzweig MC, Han H, Sanchez M, Honjo T

Abstract

We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence-activated cell sorter-purified population of the human IgM+/mouse IgG+ cells expressed mRNA that consisted of properly spliced sequences of the transgenic VHDJH and the endogenous mouse C gamma genes (trans-mRNA), together with the transgenic human mu mRNA and germline transcripts of the mouse C gamma gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic mu mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region. These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction.

MeSH Terms
Animals Gene Expression Regulation Gene Rearrangement, B-Lymphocyte, Heavy Chain Genes, Immunoglobulin Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin Isotypes/genetics Lymphoma/genetics Mice Mice, Transgenic Polymerase Chain Reaction RNA Splicing RNA, Messenger/genetics
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin Isotypes RNA, Messenger
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shimizu A
Center for Molecular Biology and Genetics, Kyoto University Faculty of Medicine, Japan.
Nussenzweig M C
Han H
Sanchez M
Honjo T
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.173.6.1385
Published
1991-06-01
Pages
1385-93
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2190851
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.173.6.1385 PMC Full Text View journal details
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