Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands

Michael Klemsz, L. B. Justement, E. Palmer, J. C. Cambier

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The data presented here indicate that both membrane Ig and IL-4 receptors transduce signals across the plasma membrane of quiescent B cells, which results in the induction of c-fos and c-myc proto-oncogene mRNA expression. Monoclonal anti-Ig antibodies with specificity for μ, δ, or κ chains, regardless of mitogenicity, induced increased c-fos and c-myc mRNA expression with kinetics and magnitude similar to that observed following stimulation of B cells with IL-4. Maximal levels of c-fos mRNA, approximately 30-fold over background, were observed 30 min after stimulation. Maximal levels of c-myc mRNA, approximately 10-fold over background, were observed 60 min after stimulation. Phorbol myristate acetate alone induced expression of these two oncogenes in a similar fashion, suggesting that protein kinase C may be involved in the regulation of their expression following anti-Ig crosslinking. Ionomycin induced only a small increase in c-myc and c-fos message (three- to four-fold), and did not synergize with phorbol myristate acetate, suggesting that the membrane Ig-mediated calcium mobilization may not play a major role in regulation of c-myc or c-fos expression in mouse B cells. In vitro nuclear run-on analyses indicate that c-myc expression is primarily regulated post-transcriptionally, whereas c-fos expression is regulated at the level of transcription. Anti-sense transcription was found to be constitutive for both the c-myc and C-fos loci and was further induced by anti-Ig and IL-4, suggesting an additional mechanism for regulation of these genes. The observation that both anti-Ig and IL-4 regulate the expression of c-fos and c-myc suggests that multiple second messenger generating systems regulate the expression of these oncogenes in normal B cells and that their expression may be necessary, but is not sufficient to drive quiescent B cells into cell cycle.

Original languageEnglish (US)
Pages (from-to)1032-1039
Number of pages8
JournalJournal of Immunology
Volume143
Issue number3
StatePublished - 1989
Externally publishedYes

Fingerprint

Interleukin-4
Immunoglobulins
B-Lymphocytes
Ligands
Messenger RNA
Tetradecanoylphorbol Acetate
Oncogenes
Interleukin-4 Receptors
Ionomycin
myc Genes
Membranes
Antibody Specificity
Second Messenger Systems
Protein Kinase C
Anti-Idiotypic Antibodies
Cell Cycle
Monoclonal Antibodies
Cell Membrane
Calcium
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands. / Klemsz, Michael; Justement, L. B.; Palmer, E.; Cambier, J. C.

In: Journal of Immunology, Vol. 143, No. 3, 1989, p. 1032-1039.

Research output: Contribution to journalArticle

Klemsz, Michael ; Justement, L. B. ; Palmer, E. ; Cambier, J. C. / Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands. In: Journal of Immunology. 1989 ; Vol. 143, No. 3. pp. 1032-1039.
@article{0df1e33cba554f61af8ed2224df821f1,
title = "Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands",
abstract = "The data presented here indicate that both membrane Ig and IL-4 receptors transduce signals across the plasma membrane of quiescent B cells, which results in the induction of c-fos and c-myc proto-oncogene mRNA expression. Monoclonal anti-Ig antibodies with specificity for μ, δ, or κ chains, regardless of mitogenicity, induced increased c-fos and c-myc mRNA expression with kinetics and magnitude similar to that observed following stimulation of B cells with IL-4. Maximal levels of c-fos mRNA, approximately 30-fold over background, were observed 30 min after stimulation. Maximal levels of c-myc mRNA, approximately 10-fold over background, were observed 60 min after stimulation. Phorbol myristate acetate alone induced expression of these two oncogenes in a similar fashion, suggesting that protein kinase C may be involved in the regulation of their expression following anti-Ig crosslinking. Ionomycin induced only a small increase in c-myc and c-fos message (three- to four-fold), and did not synergize with phorbol myristate acetate, suggesting that the membrane Ig-mediated calcium mobilization may not play a major role in regulation of c-myc or c-fos expression in mouse B cells. In vitro nuclear run-on analyses indicate that c-myc expression is primarily regulated post-transcriptionally, whereas c-fos expression is regulated at the level of transcription. Anti-sense transcription was found to be constitutive for both the c-myc and C-fos loci and was further induced by anti-Ig and IL-4, suggesting an additional mechanism for regulation of these genes. The observation that both anti-Ig and IL-4 regulate the expression of c-fos and c-myc suggests that multiple second messenger generating systems regulate the expression of these oncogenes in normal B cells and that their expression may be necessary, but is not sufficient to drive quiescent B cells into cell cycle.",
author = "Michael Klemsz and Justement, {L. B.} and E. Palmer and Cambier, {J. C.}",
year = "1989",
language = "English (US)",
volume = "143",
pages = "1032--1039",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands

AU - Klemsz, Michael

AU - Justement, L. B.

AU - Palmer, E.

AU - Cambier, J. C.

PY - 1989

Y1 - 1989

N2 - The data presented here indicate that both membrane Ig and IL-4 receptors transduce signals across the plasma membrane of quiescent B cells, which results in the induction of c-fos and c-myc proto-oncogene mRNA expression. Monoclonal anti-Ig antibodies with specificity for μ, δ, or κ chains, regardless of mitogenicity, induced increased c-fos and c-myc mRNA expression with kinetics and magnitude similar to that observed following stimulation of B cells with IL-4. Maximal levels of c-fos mRNA, approximately 30-fold over background, were observed 30 min after stimulation. Maximal levels of c-myc mRNA, approximately 10-fold over background, were observed 60 min after stimulation. Phorbol myristate acetate alone induced expression of these two oncogenes in a similar fashion, suggesting that protein kinase C may be involved in the regulation of their expression following anti-Ig crosslinking. Ionomycin induced only a small increase in c-myc and c-fos message (three- to four-fold), and did not synergize with phorbol myristate acetate, suggesting that the membrane Ig-mediated calcium mobilization may not play a major role in regulation of c-myc or c-fos expression in mouse B cells. In vitro nuclear run-on analyses indicate that c-myc expression is primarily regulated post-transcriptionally, whereas c-fos expression is regulated at the level of transcription. Anti-sense transcription was found to be constitutive for both the c-myc and C-fos loci and was further induced by anti-Ig and IL-4, suggesting an additional mechanism for regulation of these genes. The observation that both anti-Ig and IL-4 regulate the expression of c-fos and c-myc suggests that multiple second messenger generating systems regulate the expression of these oncogenes in normal B cells and that their expression may be necessary, but is not sufficient to drive quiescent B cells into cell cycle.

AB - The data presented here indicate that both membrane Ig and IL-4 receptors transduce signals across the plasma membrane of quiescent B cells, which results in the induction of c-fos and c-myc proto-oncogene mRNA expression. Monoclonal anti-Ig antibodies with specificity for μ, δ, or κ chains, regardless of mitogenicity, induced increased c-fos and c-myc mRNA expression with kinetics and magnitude similar to that observed following stimulation of B cells with IL-4. Maximal levels of c-fos mRNA, approximately 30-fold over background, were observed 30 min after stimulation. Maximal levels of c-myc mRNA, approximately 10-fold over background, were observed 60 min after stimulation. Phorbol myristate acetate alone induced expression of these two oncogenes in a similar fashion, suggesting that protein kinase C may be involved in the regulation of their expression following anti-Ig crosslinking. Ionomycin induced only a small increase in c-myc and c-fos message (three- to four-fold), and did not synergize with phorbol myristate acetate, suggesting that the membrane Ig-mediated calcium mobilization may not play a major role in regulation of c-myc or c-fos expression in mouse B cells. In vitro nuclear run-on analyses indicate that c-myc expression is primarily regulated post-transcriptionally, whereas c-fos expression is regulated at the level of transcription. Anti-sense transcription was found to be constitutive for both the c-myc and C-fos loci and was further induced by anti-Ig and IL-4, suggesting an additional mechanism for regulation of these genes. The observation that both anti-Ig and IL-4 regulate the expression of c-fos and c-myc suggests that multiple second messenger generating systems regulate the expression of these oncogenes in normal B cells and that their expression may be necessary, but is not sufficient to drive quiescent B cells into cell cycle.

UR - http://www.scopus.com/inward/record.url?scp=0024329991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024329991&partnerID=8YFLogxK

M3 - Article

C2 - 2787345

AN - SCOPUS:0024329991

VL - 143

SP - 1032

EP - 1039

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -