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PMID: 2813375 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 20 ·1989-10-00 ·Pages 8024-8

Raynal MC, Liu ZY, Hirano T, Mayer L, Kishimoto T, Chen-Kiang S

Abstract

The molecular mechanism by which interleukin 6 (IL-6) induces terminal differentiation of B cells was investigated in a subpopulation of the clonal human B-lymphoblastoid cell line CESS selected for high density of cell surface IgG1. Induction of CESS cells with IL-6 resulted in a 15-fold preferential accumulation of secreted-specific gamma 1 (gamma 1s) mRNA but not of the alternatively processed membrane-specific gamma 1 (gamma 1m) mRNA. Similarly, microseconds mRNA but not the microns mRNA of the nonproductively rearranged mu heavy-chain allele was also increased. Accompanying the differential accumulation of gamma 1s mRNA was a 4.5-fold increase in lambda light-chain mRNA, leading to secretion of IgG1. Analyses of transcription in isolated nuclei demonstrated that transcriptional activation was the primary mechanism for quantitative increase of immunoglobulin mRNAs (5.5-fold for gamma 1 and mu and at least 2-fold for lambda). Since polymerase loading is diminished by 75% before reaching the downstream gamma 1m polyadenylylation site in CESS cells, irrespective of IL-6 induction, transcriptional pausing/termination appears intrinsic and contributes to the selection of gamma 1s and gamma 1m polyadenylylation sites in activated B cells. Furthermore, differential mRNA stabilization is likely to contribute to the alteration of the gamma 1s/gamma 1m mRNA ratio at IL-6 induction.

MeSH Terms
B-Lymphocytes/drug effects,immunology Base Sequence Blotting, Northern Cell Line Gene Expression Regulation Genes, Immunoglobulin/drug effects Humans Immunoglobulin G/biosynthesis,genetics Interleukin-6/pharmacology Molecular Sequence Data Oligonucleotide Probes/chemical synthesis Plasmids RNA, Messenger/biosynthesis,drug effects,genetics Recombinant Proteins/pharmacology Transcription, Genetic/drug effects
Chemicals
Immunoglobulin G Interleukin-6 Oligonucleotide Probes RNA, Messenger Recombinant Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Raynal M C
Brookdale Center for Molecular Biology, New York, NY 10029.
Liu Z Y
Hirano T
Mayer L
Kishimoto T
Chen-Kiang S
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41 references, click to expand
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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.86.20.8024
Published
1989-10-00
Pages
8024-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298206
Subset
IM
Grants
NIAID NIH HHS · AI24404 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.20.8024 PMC Full Text View journal details
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