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Science 312 (5780): 1669-1672

Copyright © 2006 by the American Association for the Advancement of Science

Autoreactive B Cell Responses to RNA-Related Antigens Due to TLR7 Gene Duplication

Prapaporn Pisitkun,1 Jonathan A. Deane,1 Michael J. Difilippantonio,2 Tatyana Tarasenko,1 Anne B. Satterthwaite,3 Silvia Bolland1*

Abstract: Antibodies against nuclear self-antigens are characteristic of systemic autoimmunity, although mechanisms promoting their generation and selection are unclear. Here, we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased toward nucleolar antigens because of increased expression of TLR7, a single-stranded RNA-binding innate immune receptor. The TLR7 gene is duplicated in Yaa mice because of a 4-Megabase expansion of the pseudoautosomal region. These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation.

1 Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Rockville, MD 20852, USA.
2 Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
3 Department of Internal Medicine, University of Texas Southwestern, Dallas, TX 75390, USA.

* To whom correspondence should be addressed. E-mail: sbolland{at}nih.gov


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Autoimmunity Stimulated by Adoptively Transferred Dendritic Cells Is Initiated by Both {alpha}{beta} and {gamma}{delta} T Cells but Does Not Require MyD88 Signaling.
D. A. Martin, K. Zhang, J. Kenkel, G. Hughes, E. Clark, A. Davidson, and K. B. Elkon (2007)
J. Immunol. 179, 5819-5828
   Abstract »    Full Text »    PDF »
BXSB/long-lived Is a Recombinant Inbred Strain Containing Powerful Disease Suppressor Loci.
M. E. K. Haywood, L. Gabriel, S. J. Rose, N. J. Rogers, S. Izui, and B. J. Morley (2007)
J. Immunol. 179, 2428-2434
   Abstract »    Full Text »    PDF »
BAFF and MyD88 signals promote a lupuslike disease independent of T cells.
J. R. Groom, C. A. Fletcher, S. N. Walters, S. T. Grey, S. V. Watt, M. J. Sweet, M. J. Smyth, C. R. Mackay, and F. Mackay (2007)
J. Exp. Med. 204, 1959-1971
   Abstract »    Full Text »    PDF »
Murine Dendritic Cell Type I IFN Production Induced by Human IgG-RNA Immune Complexes Is IFN Regulatory Factor (IRF)5 and IRF7 Dependent and Is Required for IL-6 Production.
K. Yasuda, C. Richez, J. W. Maciaszek, N. Agrawal, S. Akira, A. Marshak-Rothstein, and I. R. Rifkin (2007)
J. Immunol. 178, 6876-6885
   Abstract »    Full Text »    PDF »
Inhibition of Toll-Like Receptor-7 (TLR-7) or TLR-7 plus TLR-9 Attenuates Glomerulonephritis and Lung Injury in Experimental Lupus.
R. D. Pawar, A. Ramanjaneyulu, O. P. Kulkarni, M. Lech, S. Segerer, and H.-J. Anders (2007)
J. Am. Soc. Nephrol. 18, 1721-1731
   Abstract »    Full Text »    PDF »
The Bxs6 Locus of BXSB Mice Is Sufficient for High-Level Expression of gp70 and the Production of gp70 Immune Complexes.
J. Rankin, J. J. Boyle, S. J. Rose, L. Gabriel, M. Lewis, V. Thiruudaian, N. J. Rogers, S. Izui, and B. J. Morley (2007)
J. Immunol. 178, 4395-4401
   Abstract »    Full Text »    PDF »
Lupus Nephritis: Toll the Trigger!.
K. D. Smith (2006)
J. Am. Soc. Nephrol. 17, 3273-3275
   Full Text »    PDF »
Nucleic Acid-Sensing TLRs as Modifiers of Autoimmunity.
J. A. Deane and S. Bolland (2006)
J. Immunol. 177, 6573-6578
   Abstract »    Full Text »    PDF »
IMMUNOLOGY: Discriminating Microbe from Self Suffers a Double Toll..
C. C. Goodnow (2006)
Science 312, 1606-1608
   Abstract »    Full Text »    PDF »

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