ERKs induce expression of the transcriptional repressor Blimp-1 and subsequent plasma cell differentiation

Tomoharu Yasuda, Kohei Kometani, Noriko Takahashi, Yuuki Imai, Yuichi Aiba, Tomohiro Kurosaki

研究成果: ジャーナルへの寄稿記事

47 引用 (Scopus)

抄録

In immune cells, the positive role of the extracellular signal-regulated kinase (ERK) signaling pathway in cell cycle progression and survival is well established; however, it is unclear whether ERK signaling plays a role in cell differentiation. Here, we report that ERKs are essential for the differentiation of B cells into antibody-producing plasma cells and that ERKs induce the expression of Prdm1, which encodes Blimp-1, a transcriptional repressor and "master regulator" of plasma cell differentiation. Transgenic mice with conditional deletion of both ERK1 and ERK2 in germinal center (GC) B cells lacked plasma cells differentiated after GC formation, and memory B cells from these mice failed to differentiate into plasma cells. In addition, ERK1- and ERK2-deficient B cells exhibited impaired Prdm1 expression upon stimulation with antibody against CD40 in the presence of interleukin-4; conversely, enforced expression of Prdm1 in ERK1- and ERK2-deficient B cells restored the generation of plasma cells. Thus, our study suggests that cytokines stimulate ERKs to induce the production of Blimp-1 and that ERKs thereby contribute to the process of cellular differentiation.

元の言語英語
記事番号ra25
ジャーナルScience Signaling
4
発行部数169
DOI
出版物ステータス出版済み - 4 19 2011

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Airships
Plasma Cells
Cell Differentiation
B-Lymphocytes
Cells
Plasmas
Germinal Center
Extracellular Signal-Regulated MAP Kinases
Antibody-Producing Cells
Antibodies
Interleukin-4
Transgenic Mice
Cell Survival
Cell Cycle
Cytokines
Data storage equipment

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

ERKs induce expression of the transcriptional repressor Blimp-1 and subsequent plasma cell differentiation. / Yasuda, Tomoharu; Kometani, Kohei; Takahashi, Noriko; Imai, Yuuki; Aiba, Yuichi; Kurosaki, Tomohiro.

:: Science Signaling, 巻 4, 番号 169, ra25, 19.04.2011.

研究成果: ジャーナルへの寄稿記事

Yasuda, Tomoharu ; Kometani, Kohei ; Takahashi, Noriko ; Imai, Yuuki ; Aiba, Yuichi ; Kurosaki, Tomohiro. / ERKs induce expression of the transcriptional repressor Blimp-1 and subsequent plasma cell differentiation. :: Science Signaling. 2011 ; 巻 4, 番号 169.
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abstract = "In immune cells, the positive role of the extracellular signal-regulated kinase (ERK) signaling pathway in cell cycle progression and survival is well established; however, it is unclear whether ERK signaling plays a role in cell differentiation. Here, we report that ERKs are essential for the differentiation of B cells into antibody-producing plasma cells and that ERKs induce the expression of Prdm1, which encodes Blimp-1, a transcriptional repressor and {"}master regulator{"} of plasma cell differentiation. Transgenic mice with conditional deletion of both ERK1 and ERK2 in germinal center (GC) B cells lacked plasma cells differentiated after GC formation, and memory B cells from these mice failed to differentiate into plasma cells. In addition, ERK1- and ERK2-deficient B cells exhibited impaired Prdm1 expression upon stimulation with antibody against CD40 in the presence of interleukin-4; conversely, enforced expression of Prdm1 in ERK1- and ERK2-deficient B cells restored the generation of plasma cells. Thus, our study suggests that cytokines stimulate ERKs to induce the production of Blimp-1 and that ERKs thereby contribute to the process of cellular differentiation.",
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AU - Yasuda, Tomoharu

AU - Kometani, Kohei

AU - Takahashi, Noriko

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AU - Aiba, Yuichi

AU - Kurosaki, Tomohiro

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