IFN-γ represses ε germline transcription and subsequently down-regulates switch recombination to ε

Lixing Xu, Paul B Rothman

Research output: Contribution to journalArticle

Abstract

Cytoklnes have the ability to regulate the isotypes of antibodies produced during an Immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-γ has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to εthrough Its ability to specifically induce germline ε transcripts. Germline εtranscription appears to target class-switch recombination to the εlocus. However, the mechanism by which IFN-γ Inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-γ and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-γ suppresses the IL-4 Induction of germline εtranscripts. In transient transfection assays, the IL-4 Induction of transcription Imparted by the minimal 179 bp germline εpromoter Is repressed by IFN-γ. Utilizing a digestion circularization -polymerase chain reaction assay we show that IL-4 Induces switch recombination to ε, while IFN-γ suppresses switch recombination to ε. These studies support a model that, through their differential effects on a cis-controlllng element that regulates germline εtranscription, IL-4 and IFN-γ are able to modulate B cell switch recombination to εin a coordinated manner.

Original languageEnglish (US)
Pages (from-to)515-521
Number of pages7
JournalInternational Immunology
Volume6
Issue number4
DOIs
StatePublished - Apr 1994
Externally publishedYes

Fingerprint

Transcription
Recombination
Interleukin-4
Genetic Recombination
B Cells
Switch
Proof by induction
Down-Regulation
Switches
Cells
Assays
Cell Differentiation
Polymerase Chain Reaction
B-Lymphocytes
Polymerase chain reaction
Immune Response
Antibody
Promoter
Antibodies
Immunoglobulin E

Keywords

  • Class-switching
  • Cytokine
  • Immunoglobulin
  • Interleukin-4

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Transplantation
  • Immunology

Cite this

IFN-γ represses ε germline transcription and subsequently down-regulates switch recombination to ε. / Xu, Lixing; Rothman, Paul B.

In: International Immunology, Vol. 6, No. 4, 04.1994, p. 515-521.

Research output: Contribution to journalArticle

@article{9220910f27e34232a8fb5d20155ada6e,
title = "IFN-γ represses ε germline transcription and subsequently down-regulates switch recombination to ε",
abstract = "Cytoklnes have the ability to regulate the isotypes of antibodies produced during an Immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-γ has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to εthrough Its ability to specifically induce germline ε transcripts. Germline εtranscription appears to target class-switch recombination to the εlocus. However, the mechanism by which IFN-γ Inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-γ and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-γ suppresses the IL-4 Induction of germline εtranscripts. In transient transfection assays, the IL-4 Induction of transcription Imparted by the minimal 179 bp germline εpromoter Is repressed by IFN-γ. Utilizing a digestion circularization -polymerase chain reaction assay we show that IL-4 Induces switch recombination to ε, while IFN-γ suppresses switch recombination to ε. These studies support a model that, through their differential effects on a cis-controlllng element that regulates germline εtranscription, IL-4 and IFN-γ are able to modulate B cell switch recombination to εin a coordinated manner.",
keywords = "Class-switching, Cytokine, Immunoglobulin, Interleukin-4",
author = "Lixing Xu and Rothman, {Paul B}",
year = "1994",
month = "4",
doi = "10.1093/intimm/6.4.515",
language = "English (US)",
volume = "6",
pages = "515--521",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - IFN-γ represses ε germline transcription and subsequently down-regulates switch recombination to ε

AU - Xu, Lixing

AU - Rothman, Paul B

PY - 1994/4

Y1 - 1994/4

N2 - Cytoklnes have the ability to regulate the isotypes of antibodies produced during an Immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-γ has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to εthrough Its ability to specifically induce germline ε transcripts. Germline εtranscription appears to target class-switch recombination to the εlocus. However, the mechanism by which IFN-γ Inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-γ and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-γ suppresses the IL-4 Induction of germline εtranscripts. In transient transfection assays, the IL-4 Induction of transcription Imparted by the minimal 179 bp germline εpromoter Is repressed by IFN-γ. Utilizing a digestion circularization -polymerase chain reaction assay we show that IL-4 Induces switch recombination to ε, while IFN-γ suppresses switch recombination to ε. These studies support a model that, through their differential effects on a cis-controlllng element that regulates germline εtranscription, IL-4 and IFN-γ are able to modulate B cell switch recombination to εin a coordinated manner.

AB - Cytoklnes have the ability to regulate the isotypes of antibodies produced during an Immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-γ has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to εthrough Its ability to specifically induce germline ε transcripts. Germline εtranscription appears to target class-switch recombination to the εlocus. However, the mechanism by which IFN-γ Inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-γ and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-γ suppresses the IL-4 Induction of germline εtranscripts. In transient transfection assays, the IL-4 Induction of transcription Imparted by the minimal 179 bp germline εpromoter Is repressed by IFN-γ. Utilizing a digestion circularization -polymerase chain reaction assay we show that IL-4 Induces switch recombination to ε, while IFN-γ suppresses switch recombination to ε. These studies support a model that, through their differential effects on a cis-controlllng element that regulates germline εtranscription, IL-4 and IFN-γ are able to modulate B cell switch recombination to εin a coordinated manner.

KW - Class-switching

KW - Cytokine

KW - Immunoglobulin

KW - Interleukin-4

UR - http://www.scopus.com/inward/record.url?scp=0028177788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028177788&partnerID=8YFLogxK

U2 - 10.1093/intimm/6.4.515

DO - 10.1093/intimm/6.4.515

M3 - Article

C2 - 8018593

AN - SCOPUS:0028177788

VL - 6

SP - 515

EP - 521

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 4

ER -