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

摘要: Antibodies against nuclear self-antigens are characteristic of systemic autoimmunity, although mechanisms promoting their generation and selection unclear. Here, we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus intrinsically biased toward nucleolar antigens because increased expression TLR7, a single-stranded RNA-binding innate immune receptor. The TLR7 gene is duplicated in Yaa mice 4-Megabase expansion pseudoautosomal region. These results reveal high divergence mouse Y chromosomes represent good example copy number qualitatively altering polygenic disease manifestation.