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.