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

Publication ,  Journal Article
Wang, H; Nicholas, MW; Conway, KL; Sen, P; Diz, R; Tisch, RM; Clarke, SH
Published in: J Immunol
September 1, 2006

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.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

September 1, 2006

Volume

177

Issue

5

Start / End Page

2793 / 2802

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Toll-Like Receptors
  • Spleen
  • Ribonucleoproteins
  • Phenotype
  • NF-kappa B
  • Mice, Transgenic
  • Mice
  • Lymphocyte Activation
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
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Wang, H., Nicholas, M. W., Conway, K. L., Sen, P., Diz, R., Tisch, R. M., & Clarke, S. H. (2006). EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity. J Immunol, 177(5), 2793–2802. https://doi.org/10.4049/jimmunol.177.5.2793
Wang, Hongsheng, Matilda W. Nicholas, Kara L. Conway, Pradip Sen, Ramiro Diz, Roland M. Tisch, and Stephen H. Clarke. “EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity.J Immunol 177, no. 5 (September 1, 2006): 2793–2802. https://doi.org/10.4049/jimmunol.177.5.2793.
Wang H, Nicholas MW, Conway KL, Sen P, Diz R, Tisch RM, et al. EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity. J Immunol. 2006 Sep 1;177(5):2793–802.
Wang, Hongsheng, et al. “EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity.J Immunol, vol. 177, no. 5, Sept. 2006, pp. 2793–802. Pubmed, doi:10.4049/jimmunol.177.5.2793.
Wang H, Nicholas MW, Conway KL, Sen P, Diz R, Tisch RM, Clarke SH. EBV latent membrane protein 2A induces autoreactive B cell activation and TLR hypersensitivity. J Immunol. 2006 Sep 1;177(5):2793–2802.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

September 1, 2006

Volume

177

Issue

5

Start / End Page

2793 / 2802

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Toll-Like Receptors
  • Spleen
  • Ribonucleoproteins
  • Phenotype
  • NF-kappa B
  • Mice, Transgenic
  • Mice
  • Lymphocyte Activation
  • Immunology