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

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

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Abstract

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.

Item Type:	Article
Additional Information:	Copyright of this article belongs to American Association of Immunologists.
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	17 Feb 2012 16:43
Last Modified:	17 Feb 2012 16:43
URI:	http://crdd.osdd.net/open/id/eprint/1026

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