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PMID: 2510157 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Immunoglobulin double-isotype expression by trans-mRNA in a human immunoglobulin transgenic mouse.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 20 ·1989-10-00 ·Pages 8020-3

Shimizu A, Nussenzweig MC, Mizuta TR, Leder P, Honjo T

Abstract

We have studied immunoglobulin double-isotype expression in a transgenic mouse (TG.SA) in which expression of the endogenous immunoglobulin heavy chain locus is almost completely excluded by a nonallelic rearranged human mu transgene. By flow-cytometric analyses, we have shown that a small, but significant, portion (about 4%) of transgenic spleen cells expresses human mu (transgene) and mouse gamma (endogenous) chains when cultured in vitro with bacterial lipopolysaccharide and interleukin 4. By using amplification of cDNA by the polymerase chain reaction, followed by cloning and sequencing of the amplified cDNA fragment, we have demonstrated expression of trans-mRNA consisting of the transgenic variable and endogenous constant (gamma 1) region sequences. Such trans-mRNA could be produced by either switch recombination or trans-splicing between the transgene and endogenous sterile gamma 1-gene transcripts. These results indicate that trans-splicing might be a possible mechanism for the immunoglobulin double-isotype expression in normal B lymphocytes that have not rearranged the second expressed constant region gene.

MeSH Terms
Animals Base Sequence Exons Flow Cytometry Gene Expression Genes, Immunoglobulin Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin Isotypes/genetics Immunoglobulin mu-Chains/genetics Lymphocytes/immunology Mice Mice, Transgenic Molecular Sequence Data Polymerase Chain Reaction RNA Splicing RNA, Messenger/genetics Spleen/immunology Transcription, Genetic
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin Isotypes Immunoglobulin mu-Chains RNA, Messenger
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shimizu A
Center for Molecular Biology and Genetics, Kyoto University, Japan.
Nussenzweig M C
Mizuta T R
Leder P
Honjo T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.20.8020
Published
1989-10-00
Pages
8020-3
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298205
Subset
IM
Databases
GENBANK
M26532
External Links
PubMed source DOI: 10.1073/pnas.86.20.8020 PMC Full Text View journal details
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