Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 19 April 2011
Vol. 4, Issue 169, p. ra25
[DOI: 10.1126/scisignal.2001592]


ERKs Induce Expression of the Transcriptional Repressor Blimp-1 and Subsequent Plasma Cell Differentiation

Tomoharu Yasuda1*{dagger}, Kohei Kometani1*, Noriko Takahashi1, Yuuki Imai2{ddagger}, Yuichi Aiba1, and Tomohiro Kurosaki1,3||

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.

{dagger} Present address: Program of Cellular and Molecular Medicine, Children’s Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.

{ddagger} 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}

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).

Read the Full Text

Diacylglycerol Kinase {zeta} Limits B Cell Antigen Receptor-Dependent Activation of ERK Signaling to Inhibit Early Antibody Responses.
M. L. Wheeler, M. B. Dong, R. Brink, X.-P. Zhong, and A. L. DeFranco (2013)
Science Signaling 6, ra91
   Abstract »    Full Text »    PDF »
Ezrin Tunes the Magnitude of Humoral Immunity.
D. Pore, N. Parameswaran, K. Matsui, M. B. Stone, I. Saotome, A. I. McClatchey, S. L. Veatch, and N. Gupta (2013)
J. Immunol. 191, 4048-4058
   Abstract »    Full Text »    PDF »
Receptor Cross-Talk Spatially Restricts p-ERK during TLR4 Stimulation of Autoreactive B Cells.
S.-R. Lee, J. A. Rutan, A. J. Monteith, S. Z. Jones, S. A. Kang, K. N. Krum, M. A. Kilmon, J. R. Roques, N. J. Wagner, S. H. Clarke, et al. (2012)
J. Immunol. 189, 3859-3868
   Abstract »    Full Text »    PDF »
IL-2 Requirement for Human Plasma Cell Generation: Coupling Differentiation and Proliferation by Enhancing MAPK-ERK Signaling.
S. Le Gallou, G. Caron, C. Delaloy, D. Rossille, K. Tarte, and T. Fest (2012)
J. Immunol. 189, 161-173
   Abstract »    Full Text »    PDF »
B Cell Receptor-ERK1/2 Signal Cancels PAX5-Dependent Repression of BLIMP1 through PAX5 Phosphorylation: A Mechanism of Antigen-Triggering Plasma Cell Differentiation.
T. Yasuda, F. Hayakawa, S. Kurahashi, K. Sugimoto, Y. Minami, A. Tomita, and T. Naoe (2012)
J. Immunol. 188, 6127-6134
   Abstract »    Full Text »    PDF »
Antigen Feast or Famine.
M. L. Dustin and M. Meyer-Hermann (2012)
Science 335, 408-409
   Abstract »    Full Text »    PDF »
pERKing Up the BLIMP in Plasma Cell Differentiation.
D. M. Allman and M. P. Cancro (2011)
Science Signaling 4, pe21
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882