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The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells

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The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells. / Grötsch, Bettina; Brachs, Sebastian; Lang, Christiane; Luther, Julia; Derer, Anja; Schlötzer-Schrehardt, Ursula; Bozec, Aline; Fillatreau, Simon; Berberich, Ingolf; Hobeika, Elias; Reth, Michael; Wagner, Erwin F; Schett, Georg; Mielenz, Dirk; David, Jean-Pierre.

In: J EXP MED, Vol. 211, No. 11, 20.10.2014, p. 2199-2212.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Grötsch, B, Brachs, S, Lang, C, Luther, J, Derer, A, Schlötzer-Schrehardt, U, Bozec, A, Fillatreau, S, Berberich, I, Hobeika, E, Reth, M, Wagner, EF, Schett, G, Mielenz, D & David, J-P 2014, 'The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells', J EXP MED, vol. 211, no. 11, pp. 2199-2212. https://doi.org/10.1084/jem.20130795

APA

Grötsch, B., Brachs, S., Lang, C., Luther, J., Derer, A., Schlötzer-Schrehardt, U., Bozec, A., Fillatreau, S., Berberich, I., Hobeika, E., Reth, M., Wagner, E. F., Schett, G., Mielenz, D., & David, J-P. (2014). The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells. J EXP MED, 211(11), 2199-2212. https://doi.org/10.1084/jem.20130795

Vancouver

Grötsch B, Brachs S, Lang C, Luther J, Derer A, Schlötzer-Schrehardt U et al. The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells. J EXP MED. 2014 Oct 20;211(11):2199-2212. https://doi.org/10.1084/jem.20130795

Bibtex

@article{0d56b6e068b144d5ba290e068f2adef6,
title = "The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells",
abstract = "The cornerstone of humoral immunity is the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1). Proliferation of activated B cells is required to foster Blimp1 expression but needs to be terminated to avoid overshooting immune reactions. Activator protein 1 (AP-1) transcription factors become quickly up-regulated upon B cell activation. We demonstrate that Fra1, a Fos member of AP-1, enhances activation-induced cell death upon induction in activated B cells. Moreover, mice with B cell-specific deletion of Fra1 show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production, which cannot be rescued by Bcl2. On the molecular level, Fra1 represses Blimp1 expression and interferes with binding of the activating AP-1 member c-Fos to the Blimp1 promoter. Conversely, overexpression of c-Fos in Fra1 transgenic B cells releases Blimp1 repression. As Fra1 lacks transcriptional transactivation domains, we propose that Fra1 inhibits Blimp1 expression and negatively controls plasma cell differentiation through binding to the Blimp1 promoter. In summary, we demonstrate that Fra1 negatively controls plasma cell differentiation by repressing Blimp1 expression.",
keywords = "Animals, Apoptosis, B-Lymphocytes, Cell Differentiation, Gene Expression Regulation, Immunity, Humoral, Immunomodulation, Lymphocyte Activation, Mice, Mice, Transgenic, Plasma Cells, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-fos, Transcription Factors",
author = "Bettina Gr{\"o}tsch and Sebastian Brachs and Christiane Lang and Julia Luther and Anja Derer and Ursula Schl{\"o}tzer-Schrehardt and Aline Bozec and Simon Fillatreau and Ingolf Berberich and Elias Hobeika and Michael Reth and Wagner, {Erwin F} and Georg Schett and Dirk Mielenz and Jean-Pierre David",
note = "{\textcopyright} 2014 Gr{\"o}tsch et al.",
year = "2014",
month = oct,
day = "20",
doi = "10.1084/jem.20130795",
language = "English",
volume = "211",
pages = "2199--2212",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "11",

}

RIS

TY - JOUR

T1 - The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells

AU - Grötsch, Bettina

AU - Brachs, Sebastian

AU - Lang, Christiane

AU - Luther, Julia

AU - Derer, Anja

AU - Schlötzer-Schrehardt, Ursula

AU - Bozec, Aline

AU - Fillatreau, Simon

AU - Berberich, Ingolf

AU - Hobeika, Elias

AU - Reth, Michael

AU - Wagner, Erwin F

AU - Schett, Georg

AU - Mielenz, Dirk

AU - David, Jean-Pierre

N1 - © 2014 Grötsch et al.

PY - 2014/10/20

Y1 - 2014/10/20

N2 - The cornerstone of humoral immunity is the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1). Proliferation of activated B cells is required to foster Blimp1 expression but needs to be terminated to avoid overshooting immune reactions. Activator protein 1 (AP-1) transcription factors become quickly up-regulated upon B cell activation. We demonstrate that Fra1, a Fos member of AP-1, enhances activation-induced cell death upon induction in activated B cells. Moreover, mice with B cell-specific deletion of Fra1 show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production, which cannot be rescued by Bcl2. On the molecular level, Fra1 represses Blimp1 expression and interferes with binding of the activating AP-1 member c-Fos to the Blimp1 promoter. Conversely, overexpression of c-Fos in Fra1 transgenic B cells releases Blimp1 repression. As Fra1 lacks transcriptional transactivation domains, we propose that Fra1 inhibits Blimp1 expression and negatively controls plasma cell differentiation through binding to the Blimp1 promoter. In summary, we demonstrate that Fra1 negatively controls plasma cell differentiation by repressing Blimp1 expression.

AB - The cornerstone of humoral immunity is the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1). Proliferation of activated B cells is required to foster Blimp1 expression but needs to be terminated to avoid overshooting immune reactions. Activator protein 1 (AP-1) transcription factors become quickly up-regulated upon B cell activation. We demonstrate that Fra1, a Fos member of AP-1, enhances activation-induced cell death upon induction in activated B cells. Moreover, mice with B cell-specific deletion of Fra1 show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production, which cannot be rescued by Bcl2. On the molecular level, Fra1 represses Blimp1 expression and interferes with binding of the activating AP-1 member c-Fos to the Blimp1 promoter. Conversely, overexpression of c-Fos in Fra1 transgenic B cells releases Blimp1 repression. As Fra1 lacks transcriptional transactivation domains, we propose that Fra1 inhibits Blimp1 expression and negatively controls plasma cell differentiation through binding to the Blimp1 promoter. In summary, we demonstrate that Fra1 negatively controls plasma cell differentiation by repressing Blimp1 expression.

KW - Animals

KW - Apoptosis

KW - B-Lymphocytes

KW - Cell Differentiation

KW - Gene Expression Regulation

KW - Immunity, Humoral

KW - Immunomodulation

KW - Lymphocyte Activation

KW - Mice

KW - Mice, Transgenic

KW - Plasma Cells

KW - Promoter Regions, Genetic

KW - Protein Binding

KW - Proto-Oncogene Proteins c-fos

KW - Transcription Factors

U2 - 10.1084/jem.20130795

DO - 10.1084/jem.20130795

M3 - SCORING: Journal article

C2 - 25288397

VL - 211

SP - 2199

EP - 2212

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 11

ER -