Pisitkun Prapaporn, Deane Jonathan A, Difilippantonio Michael J, Tarasenko Tatyana, Satterthwaite Anne B, Bolland Silvia
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Rockville, MD 20852, USA.
Science. 2006 Jun 16;312(5780):1669-72. doi: 10.1126/science.1124978. Epub 2006 May 18.
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.
针对核自身抗原的抗体是系统性自身免疫的特征，尽管促进其产生和选择的机制尚不清楚。在此，我们报告称，含有Y连锁自身免疫加速器（Yaa）基因座的B细胞由于单链RNA结合先天免疫受体TLR7表达增加而内在地偏向核仁抗原。由于假常染色体区域的4兆碱基扩展，TLR7基因在Yaa小鼠中发生了复制。这些结果揭示了小鼠Y染色体的高度差异，并代表了基因拷贝数在质量上改变多基因疾病表现的一个很好的例子。
