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

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

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.

Original languageEnglish
Article numberra25
JournalScience Signaling
Volume4
Issue number169
DOIs
Publication statusPublished - Apr 19 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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