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      Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication.

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          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.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Jun 16 2006
          : 312
          : 5780
          Affiliations
          [1 ] Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Rockville, MD 20852, USA.
          Article
          1124978
          10.1126/science.1124978
          16709748
          5e13de33-9ea6-4607-b4bb-57d8ec82f404
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