Regulation of B cell tolerance by the lupus susceptibility gene Ly108
Regulation of B cell tolerance by the lupus susceptibility gene Ly108
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DOI：
10.1126/science.1125893
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发表时间：
2006-06-16
期刊：
影响因子：
56.9
通讯作者：
Mohan, Chandra
中科院分区：
文献类型：
--
作者：
Kumar, Kirthi Raman;Li, Liunan;Mohan, Chandra
小鼠1号染色体上自身免疫性疾病狼疮的易感基因座Sle 1（z）/Sle 1b（z）和直系同源人类基因座与染色质自身抗体的产生相关。我们报道了Sle 1（z）/Sle 1 B（z）的存在损害了B细胞的无反应性、受体的修改和缺失。SLAM共刺激分子家族的成员构成了Sle 1 B（z）的主要候选者，其中Ly 108基因的Ly108.1同种型在来自狼疮倾向B6的未成熟B细胞中表达最高。Sle 1（z）小鼠。正常的Ly108.2等位基因，而不是狼疮相关的Ly108.1等位基因，被发现敏感的未成熟的B细胞删除和RAG重新表达。作为耐受检查点的潜在调节剂，Ly 108可以审查自身反应性B细胞，从而防止自身免疫。
The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1(z)/Sle1b(z), and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1(z)/Sle1b(z) impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1b(z), among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6. Sle1(z) mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.