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

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Science  16 Jun 2006:
Vol. 312, Issue 5780, pp. 1669-1672
DOI: 10.1126/science.1124978

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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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