%A Hongsheng Wang
%A Matilda W Nicholas
%A Kara L Conway
%A Pradip Sen
%A Ramiro Diz
%A Roland M Tisch
%A Stephen H Clarke
%O Copyright of this article belongs to American Association of Immunologists.
%J Journal of immunology (Baltimore, Md. : 1950)
%T EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity.
%X 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.
%N 5
%P 2793-802
%V 177
%D 2006
%I American Association of Immunologists
%L open1026