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Science 8 October 1999:
Vol. 286. no. 5438, pp. 300 - 303
DOI: 10.1126/science.286.5438.300
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Reports

Mimicry of CD40 Signals by Epstein-Barr Virus LMP1 in B Lymphocyte Responses

Junji Uchida, 1* Teruhito Yasui, 1* Yuko Takaoka-Shichijo, 1 Masaaki Muraoka, 1 Wanla Kulwichit, 2 Nancy Raab-Traub, 2 Hitoshi Kikutani 1dagger

The effect of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) on the activation and differentiation of normal B cells was investigated. B cells of transgenic mice expressing LMP1 under the control of immunoglobulin promoter/enhancer displayed enhanced expression of activation antigens and spontaneously proliferated and produced antibody. Humoral immune responses of LMP1 transgenic mice in CD40-deficient or normal backgrounds revealed that LMP1 mimics CD40 signals to induce extrafollicular B cell differentiation but, unlike CD40, blocks germinal center formation. Thus, these specific properties of LMP1 may determine the site of primary B cell infection and the state of infection in the natural course of EBV infection, whereas subsequent loss of LMP1 expression may affect the site of persistent latent infection.

1 Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
2 Line-berger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: kikutani{at}ragtime.biken.osaka-u.ac.jp

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