Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication
Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication
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DOI：
10.1126/science.1124978
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发表时间：
2006-06-16
期刊：
影响因子：
56.9
通讯作者：
Bolland, Silvia
中科院分区：
文献类型：
--
作者：
Pisitkun, Prapaporn;Deane, Jonathan A.;Bolland, Silvia
抗核自身抗原抗体是全身性自身免疫的特征，尽管促进其产生和选择的机制尚不清楚。在这里，我们报告了含有Y连锁自身免疫加速器(YAA)基因的B细胞由于TLR7的表达增加而固有地偏向核仁抗原，TLR7是一种单链RNA结合的先天免疫受体。TLR7基因在YAA小鼠中复制，因为假常染色体区域有4兆碱基的扩张。这些结果揭示了小鼠Y染色体的高度分化，并代表了基因拷贝数定性改变多基因疾病表现的一个很好的例子。
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.