Mitogen- and IL-4-regulated expression of germ-line Ig γ2b transcripts: Evidence for directed heavy chain class switching

Stuart Lutzker; Paul Rothman; Roberta Pollock; Robert Coffman; Frederick W. Alt

doi:10.1016/0092-8674(88)90379-0

Mitogen- and IL-4-regulated expression of germ-line Ig γ2b transcripts: Evidence for directed heavy chain class switching

Stuart Lutzker, Paul Rothman, Roberta Pollock, Robert Coffman, Frederick W. Alt

Research output: Contribution to journal › Article › peer-review

226 Scopus citations

Abstract

Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (C_H) genes. This class switch involves recombination between switch regions located upstream of the germ-line C_H genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line γ2b locus and γ2b class switching. In both cell types, LPS induces transcription specifically through the germ-line γ2b locus before γ2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line γ2b transcripts in spleen cells and correspondingly abrogates switching to this C_H gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line C_H genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.

Original language	English (US)
Pages (from-to)	177-184
Number of pages	8
Journal	Cell
Volume	53
Issue number	2
DOIs	https://doi.org/10.1016/0092-8674(88)90379-0
State	Published - Apr 22 1988
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/0092-8674(88)90379-0

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@article{0d773f33cb9748eda71e4746261dfe05,

title = "Mitogen- and IL-4-regulated expression of germ-line Ig γ2b transcripts: Evidence for directed heavy chain class switching",

abstract = "Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (CH) genes. This class switch involves recombination between switch regions located upstream of the germ-line CH genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line γ2b locus and γ2b class switching. In both cell types, LPS induces transcription specifically through the germ-line γ2b locus before γ2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line γ2b transcripts in spleen cells and correspondingly abrogates switching to this CH gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line CH genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.",

author = "Stuart Lutzker and Paul Rothman and Roberta Pollock and Robert Coffman and Alt, {Frederick W.}",

note = "Funding Information: The authors would llke to express their appreclatlon to Keith Blackwell for crItIcal evaluation of this manuscript, Barbara Malynn for many thoughtful discussions, Ira Schberen for assistance with the FACS analyses. and Robert Kasteleln and Brian Castle for preparation of the recombinant murine IL-4. We would also llke lo acknowleoge gratefully the supporl of the Howard Huyhes Medlcal Inslttute, grants from the National Institutes of Health (NIH) (Al-20047 and CA-40427). and awards from the Mallmckrodt and Hirsch1 Foundations (to F. W A.) S L. was supported by NIH training grant GM-07367, P R. by a Physician Scientist Award, and R. P by a Special Fellowship from the Leukemia Society of America.",

year = "1988",

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doi = "10.1016/0092-8674(88)90379-0",

language = "English (US)",

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T1 - Mitogen- and IL-4-regulated expression of germ-line Ig γ2b transcripts

T2 - Evidence for directed heavy chain class switching

AU - Lutzker, Stuart

AU - Rothman, Paul

AU - Pollock, Roberta

AU - Coffman, Robert

AU - Alt, Frederick W.

N1 - Funding Information: The authors would llke to express their appreclatlon to Keith Blackwell for crItIcal evaluation of this manuscript, Barbara Malynn for many thoughtful discussions, Ira Schberen for assistance with the FACS analyses. and Robert Kasteleln and Brian Castle for preparation of the recombinant murine IL-4. We would also llke lo acknowleoge gratefully the supporl of the Howard Huyhes Medlcal Inslttute, grants from the National Institutes of Health (NIH) (Al-20047 and CA-40427). and awards from the Mallmckrodt and Hirsch1 Foundations (to F. W A.) S L. was supported by NIH training grant GM-07367, P R. by a Physician Scientist Award, and R. P by a Special Fellowship from the Leukemia Society of America.

PY - 1988/4/22

Y1 - 1988/4/22

N2 - Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (CH) genes. This class switch involves recombination between switch regions located upstream of the germ-line CH genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line γ2b locus and γ2b class switching. In both cell types, LPS induces transcription specifically through the germ-line γ2b locus before γ2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line γ2b transcripts in spleen cells and correspondingly abrogates switching to this CH gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line CH genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.

AB - Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (CH) genes. This class switch involves recombination between switch regions located upstream of the germ-line CH genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line γ2b locus and γ2b class switching. In both cell types, LPS induces transcription specifically through the germ-line γ2b locus before γ2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line γ2b transcripts in spleen cells and correspondingly abrogates switching to this CH gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line CH genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.

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Mitogen- and IL-4-regulated expression of germ-line Ig γ2b transcripts: Evidence for directed heavy chain class switching

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