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EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity.
 
Creator Wang, Hongsheng
Nicholas, Matilda W
Conway, Kara L
Sen, Pradip
Diz, Ramiro
Tisch, Roland M
Clarke, Stephen H
 
Subject QR180 Immunology
 
Description EBV is associated with systemic lupus erythematosus (SLE), but how it might contribute to the etiology is not clear. Since EBV-encoded latent membrane protein 2A (LMP2A) interferes with normal B cell differentiation and function, we sought to determine its effect on B cell tolerance. Mice transgenic for both LMP2A and the Ig transgene 2-12H specific for the ribonucleoprotein Smith (Sm), a target of the immune system in SLE, develop a spontaneous anti-Sm response. LMP2A allows anti-Sm B cells to overcome the regulatory checkpoint at the early preplasma cell stage by a self-Ag-dependent mechanism. LMP2A induces a heightened sensitivity to TLR ligand stimulation, resulting in increased proliferation or Ab-secreting cell differentiation or both. Thus, we propose a model whereby LMP2A induces hypersensitivity to TLR stimulation, leading to activation of anti-Sm B cells through the BCR/TLR pathway. These data further implicate TLRs in the etiology of SLE and suggest a mechanistic link between EBV infection and SLE.
 
Publisher American Association of Immunologists
 
Date 2006-09-01
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1026/1/sen2006.1.pdf
Wang, Hongsheng and Nicholas, Matilda W and Conway, Kara L and Sen, Pradip and Diz, Ramiro and Tisch, Roland M and Clarke, Stephen H (2006) EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity. Journal of immunology (Baltimore, Md. : 1950), 177 (5). pp. 2793-802. ISSN 0022-1767
 
Relation http://www.jimmunol.org/content/177/5/2793.full.pdf+html
http://crdd.osdd.net/open/1026/