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RIKEN: Signaling Pathway Reveals Mechanism for B Cell Differentiation in Immune Response

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Tokyo, Apr 22, 2011 (JCN Newswire) - An article in Science Signaling by researchers at the RIKEN Research Center for Allergy and Immunology (RCAI) has clarified for the first time the mechanism governing differentiation of B cells into antibody-producing plasma cells. The finding establishes a role for the extracellular signal-regulated kinase (ERK) signaling pathway in B cell differentiation, a key step toward the development of B cell-targeted drugs for treatment of autoimmune diseases and allergies.

As the only cells in the body that produce antibodies, B cells play an essential role in the immune system's defense against bacteria and viruses. Differentiation of B cells into antibody-producing plasma cells is central to this role, initiating the production of antibodies whose targeted binding mechanism enables the immune system to identify and neutralize foreign objects. The mechanism underlying this differentiation process, however, remains unknown.

To better understand this mechanism, the research group focused on the signaling of the extracellular signal-regulated kinases (ERK), intracellular signaling molecules known to play an important role in the cell cycle and survival of immune cells. Hoping to glean insights into the role of ERKs in B cell differentiation into plasma cells, the researchers generated mice deficient in two different ERKs, ERK1 and ERK2, and studied the effect of this deficiency on the fate of B cells.

What they found confirmed that ERKs are in fact essential to B cell differentiation: B cells in mice without these key molecules were unable to form plasma cells (Figure 1). The researchers further traced this observation to a gene called Prdm1 encoding the protein BLIMP-1, increased expression of which leads to differentiation and proliferation of plasma cells in B cell immune response (Figure 2). ERKs, they discovered, phosphorylate the transcription factor Elk1, which leads to expression of Blimp-1 (Figure 3).

By elucidating the role of ERKs in B cell differentiation, the current research provides valuable insight into a little-understood area of immune response, promising advances in drug discovery and offering hope to autoimmune disease and allergy sufferers around the world.

Reference:
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). DOI: 10.1126/scisignal.2001592

Press document (with Figures):
http://www.acnnewswire.com/pdf/riken/riken-4-21.pdf

About the RIKEN Research Center for Allergy and Immunology

Our immune system forms a complex line of defense that normally protects us from diseases. Sometimes, however, the immune system becomes abnormal or fails. As a result, serious ailments, such allergic disorders, autoimmune diseases, graft-versus-host disease, AIDS, and cancer have emerged as important social and medical problems worldwide.

As a unique research institute different from universities or corporations, the RIKEN Research Center for Allergy and Immunology (RCAI) focuses on the development of innovative research platforms that will greatly contribute to the advances in science and medicine. These research platforms are utilized by researchers and clinicians in various universities and companies, and we work together with them to reach our final goal, to make lasting contributions to the people, medical care and society, by solving immunological problems. For more information, please see: http://www.rcai.riken.jp/english/.

Contact:

Tomohiro Kurosaki
Laboratory for Lymphocyte Differentiation
RIKEN Research Center for Allergy and Immunology
Tel: +81-45-503-7019 / Fax: +81-45-503-7018

Ms. Tomoko Ikawa (PI officer)
Global Relations Office
RIKEN
Tel: +81-48-462-1225 / Fax: +81-48-463-3687
Email: koho@riken.jp

Distributed for RIKEN by ResearchSEA.

About RIKEN Institute

RIKEN, one of Japan's leading research institutes, conducts basic and applied experimental research in a wide range of science and technology fields including physics, chemistry, medical science, biology and engineering. Initially established as a private research foundation in Tokyo in 1917, RIKEN became an independent administrative institution in 2003. For more information, visit www.riken.jp/engn/index.html.

Contact:


Tomohiro Kurosaki
Laboratory for Lymphocyte Differentiation
RIKEN Research Center for Allergy and Immunology
Tel: +81-45-503-7019 / Fax: +81-45-503-7018

Ms. Tomoko Ikawa (PI officer) 
Global Relations Office 
RIKEN
Tel: +81-48-462-1225 / Fax: +81-48-463-3687
Email: koho@riken.jp

Apr 22, 2011
Source: RIKEN Institute
RIKEN Institute
From the Japan Corporate News Network
http://www.japancorp.net
Topic: Research and development