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1 Laboratory for Lymphocyte Differentiation, Research Center for Allergy and Immunology, RIKEN, Yokohama, Kanagawa 230-0045, Japan. 2 Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. 3 Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
* These authors contributed equally to this work.
Present address: Program of Cellular and Molecular Medicine, Children’s Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Present address: Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
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.
|| To whom correspondence should be addressed. E-mail: kurosaki{at}rcai.riken.jp
Citation: T. Yasuda, K. Kometani, N. Takahashi, Y. Imai, Y. Aiba, T. Kurosaki, ERKs Induce Expression of the Transcriptional Repressor Blimp-1 and Subsequent Plasma Cell Differentiation. Sci. Signal.4, ra25 (2011).
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,
Kohei Kometani1
,
Yuichi Aiba1, and
Tomohiro Kurosaki1,3
Present address: Program of Cellular and Molecular Medicine, Children’s Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Present address: Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
