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The EBV transforming protein, latent membrane protein 1, mimics and cooperates with CD40 signaling in B lymphocytes
Journal article   Peer reviewed

The EBV transforming protein, latent membrane protein 1, mimics and cooperates with CD40 signaling in B lymphocytes

Lisa K Busch and Gail A Bishop
The Journal of immunology (1950), Vol.162(5), pp.2555-2561
03/01/1999
DOI: 10.4049/jimmunol.162.5.2555
PMID: 10072495

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Abstract

Latent membrane protein 1 (LMP1) is required for EBV-induced immortalization of human B cells, and expression of the protein in the absence of other viral proteins leads to an activated phenotype in B cells. It has been well documented that LMP1 causes B cells to up-regulate adhesion molecules, such as LFA-1 and ICAM-1, and coactivation molecules, such as B7-1 and CD23, as well as to activate NF-kappaB. Ligation of the endogenous B cell CD40 molecule also induces these and other activated phenotypic changes. Here, we report that expression of LMP1 also activates B cells to secrete Ig and IL-6 and rescues them from B cell receptor-mediated growth arrest analogous to CD40 signaling. Furthermore, an HLA-A2LMP1 chimeric construct demonstrates that the oligomerization of the carboxyl-terminal 200 amino acids of LMP1 is sufficient for B cell signaling. Finally, we demonstrate that LMP1 and CD40 signaling pathways interact cooperatively in inducing B cell effector functions.
 Oncogene Proteins, Viral - physiology CD40 Antigens - physiology Animals Lymphocyte Function-Associated Antigen-1 - biosynthesis Intercellular Adhesion Molecule-1 - biosynthesis B-Lymphocytes - physiology NF-kappa B - metabolism Receptors, Antigen, B-Cell - physiology Mice Tumor Cells, Cultured Viral Matrix Proteins - physiology Interleukin-6 - secretion

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