Synthesis of germ-line γ1 immunoglobulin heavy-chain transcripts in resting B cells

Induction by interleukin 4 and inhibition by interferon γ

M. T. Berton, J. W. Uhr, E. S. Vitetta

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line γ1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon γ. IL-4 alone is capable of inducing the expression of germ-line γ1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional γl mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the γl constant-region exon(s). These data strongly support the 'accessibility' model for the regulation of isotype switching and suggests that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.

Original languageEnglish (US)
Pages (from-to)2829-2833
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number8
StatePublished - 1989

Fingerprint

Immunoglobulin Heavy Chains
Germ Cells
Interleukin-4
Interferons
B-Lymphocytes
Immunoglobulin Class Switching
Exons
Recombinases
Lymphokines
Ribonucleases
Immunoglobulin E
Transcriptional Activation
Lipopolysaccharides
Immunoglobulin G
Messenger RNA
Membranes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{d711a8e2fa12413b8d7236cbc9d0bb7e,
title = "Synthesis of germ-line γ1 immunoglobulin heavy-chain transcripts in resting B cells: Induction by interleukin 4 and inhibition by interferon γ",
abstract = "Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line γ1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon γ. IL-4 alone is capable of inducing the expression of germ-line γ1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional γl mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the γl constant-region exon(s). These data strongly support the 'accessibility' model for the regulation of isotype switching and suggests that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.",
author = "Berton, {M. T.} and Uhr, {J. W.} and Vitetta, {E. S.}",
year = "1989",
language = "English (US)",
volume = "86",
pages = "2829--2833",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Synthesis of germ-line γ1 immunoglobulin heavy-chain transcripts in resting B cells

T2 - Induction by interleukin 4 and inhibition by interferon γ

AU - Berton, M. T.

AU - Uhr, J. W.

AU - Vitetta, E. S.

PY - 1989

Y1 - 1989

N2 - Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line γ1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon γ. IL-4 alone is capable of inducing the expression of germ-line γ1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional γl mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the γl constant-region exon(s). These data strongly support the 'accessibility' model for the regulation of isotype switching and suggests that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.

AB - Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line γ1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon γ. IL-4 alone is capable of inducing the expression of germ-line γ1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional γl mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the γl constant-region exon(s). These data strongly support the 'accessibility' model for the regulation of isotype switching and suggests that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.

UR - http://www.scopus.com/inward/record.url?scp=0344037977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344037977&partnerID=8YFLogxK

M3 - Article

VL - 86

SP - 2829

EP - 2833

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -