Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection
Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection
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DOI：
10.1016/s1074-7613(00)80554-3
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发表时间：
1998-04-01
期刊：
影响因子：
32.4
通讯作者：
Goodnow, CC
中科院分区：
文献类型：
--
作者：
Cornall, RJ;Cyster, JG;Goodnow, CC
类似系统性红斑狼疮的B淋巴细胞多动综合征是缺乏src家族激酶Lyn的小鼠的特征，Lyn不需要启动细胞抗原受体（BCR）信号传导，但却是必要的抑制成分。lyn(-/-) B细胞在有抗原的情况下具有延迟但增加的钙通量和夸张的负选择反应，而在无抗原的情况下具有自发的多活性。与无脊椎动物一样，只有一个功能等位基因的基因座的遗传效应可以用于分析小鼠的信号网络，表明BCR的负调控是一个复杂的数量性状，其中Lyn、辅助受体CD22和酪氨酸磷酸酶SHP-1都是限制因素。这一复杂性状的生化基础涉及Lyn磷酸化CD22并将SHP-1招募到CD22/BCR复合物的途径。
A B lymphocyte hyperactivity syndrome resembling systemic lupus erythematosus characterizes mice lacking the src-family kinase Lyn, Lyn is not required to initiate a cell antigen receptor (BCR) signaling but is an essential inhibitory component. lyn(-/-) B cells have a delayed but increased calcium flux and exaggerated negative selection responses in the presence of antigen and spontaneous hyperactivity in the absence of antigen. As in invertebrates, genetic effects of loci with only one functional allele can be used to analyze signaling networks in mice, demonstrating that negative regulation of the BCR is a complex quantitative trait in which Lyn, the coreceptor CD22, and the tyrosine phosphatase SHP-1 are each limiting elements. The biochemical basis of this complex trait involves a pathway requiring Lyn to phosphorylate CD22 and recruit SHP-1 to the CD22/BCR complex.