Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation Academic Article uri icon

Overview

MeSH Major

  • Gene Expression Regulation
  • Genes, Immunoglobulin
  • Immunoglobulin G
  • Interleukin-6
  • 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.

publication date

  • January 1989

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC298206

PubMed ID

  • 2813375

Additional Document Info

start page

  • 8024

end page

  • 8

volume

  • 86

number

  • 20