Title | Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation. |
Publication Type | Journal Article |
Year of Publication | 1989 |
Authors | Raynal MC, Liu ZY, Hirano T, Mayer L, Kishimoto T, Chen-Kiang S |
Journal | Proc Natl Acad Sci U S A |
Volume | 86 |
Issue | 20 |
Pagination | 8024-8 |
Date Published | 1989 Oct |
ISSN | 0027-8424 |
Keywords | B-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 |
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. |
DOI | 10.1073/pnas.86.20.8024 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 2813375 |
PubMed Central ID | PMC298206 |
Grant List | AI24404 / AI / NIAID NIH HHS / United States |
Related Faculty:
Selina Chen-Kiang, Ph.D.