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

P. Pisitkun, J. A. Deane, M. Difilippantonio, T. Tarasenko, A. Satterthwaite, S. Bolland
Published 2006 · Medicine, Biology

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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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