TY - JOUR
T1 - Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication
AU - Pisitkun, Prapaporn
AU - Deane, Jonathan A.
AU - Difilippantonio, Michael J.
AU - Tarasenko, Tatyana
AU - Satterthwaite, Anne B.
AU - Bolland, Silvia
PY - 2006/6/16
Y1 - 2006/6/16
N2 - 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.
AB - 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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U2 - 10.1126/science.1124978
DO - 10.1126/science.1124978
M3 - Article
C2 - 16709748
AN - SCOPUS:33745168605
SN - 0036-8075
VL - 312
SP - 1669
EP - 1672
JO - Science
JF - Science
IS - 5780
ER -