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

Prapaporn Pisitkun, Jonathan A. Deane, Michael J. Difilippantonio, Tatyana Tarasenko, Anne B. Satterthwaite, Silvia Bolland

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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.

Original languageEnglish (US)
Pages (from-to)1669-1672
Number of pages4
JournalScience
Volume312
Issue number5780
DOIs
StatePublished - Jun 16 2006

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Cite this

Pisitkun, P., Deane, J. A., Difilippantonio, M. J., Tarasenko, T., Satterthwaite, A. B., & Bolland, S. (2006). Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science, 312(5780), 1669-1672. https://doi.org/10.1126/science.1124978