EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity.
Journal Article (Journal Article)
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.
- Wang, H; Nicholas, MW; Conway, KL; Sen, P; Diz, R; Tisch, RM; Clarke, SH
- September 1, 2006
Volume / Issue
- 177 / 5
Start / End Page
- 2793 - 2802
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States