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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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