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

TitleInterleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation.
Publication TypeJournal Article
Year of Publication1989
AuthorsRaynal MC, Liu ZY, Hirano T, Mayer L, Kishimoto T, Chen-Kiang S
JournalProc Natl Acad Sci U S A
Date Published1989 Oct
KeywordsB-Lymphocytes, Base Sequence, Blotting, Northern, Cell Line, Gene Expression Regulation, Genes, Immunoglobulin, Humans, Immunoglobulin G, Interleukin-6, Molecular Sequence Data, Oligonucleotide Probes, Plasmids, Recombinant Proteins, RNA, Messenger, Transcription, Genetic

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.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID2813375
PubMed Central IDPMC298206
Grant ListAI24404 / AI / NIAID NIH HHS / United States
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