PROTEIN-TYROSINE-PHOSPHATASE 1C NEGATIVELY REGULATES ANTIGEN RECEPTOR SIGNALING IN B-LYMPHOCYTES AND DETERMINES THRESHOLDS FOR NEGATIVE SELECTION
PROTEIN-TYROSINE-PHOSPHATASE 1C NEGATIVELY REGULATES ANTIGEN RECEPTOR SIGNALING IN B-LYMPHOCYTES AND DETERMINES THRESHOLDS FOR NEGATIVE SELECTION
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DOI：
10.1016/1074-7613(95)90075-6
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发表时间：
1995-01-01
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：
CYSTER, JG;GOODNOW, CC
MOTHEN存活(Me(V))小鼠缺乏胞浆蛋白酪氨酸磷酸酶PTP1C，表现出严重的B细胞免疫缺陷和自身抗体产生。通过将针对特定抗原--鸡蛋溶菌酶的免疫球蛋白转基因基因培育到Me(V)小鼠体内，分析了PTP1C在细胞选择和功能中的作用。在PTP1C缺乏的B细胞中，抗原触发了细胞内钙的更大和更快的升高，表明这种磷酸酶负向调节免疫球蛋白信号。携带这种信号增强突变的自身反应性B细胞的消除是在它们的发育过程中通过结合比正常需要的更低价态的自身抗原来触发的。这些发现表明，不同的曲目审查机制的激活依赖于抗原受体信号的数量差异，其阈值由PTP1C的负调控决定。
Motheaten viable (me(v)) mice are deficient in the cytosolic protein tyrosine phosphatase, PTP1C, and exhibit severe B cell immunodeficiency and autoantibody production. The role of PTP1C in a cell selection and function was analyzed by breeding immunoglobulin transgenes specific for a defined antigen, hen egg lysozyme, into me(v) mice. Antigen triggered a greater and more rapid elevation of intracellular calcium in PTP1C-deficient B cells, indicating that this phosphatase negatively regulates immunoglobulin signaling. Elimination of self-reactive B cells carrying this signal-enhancing mutation was triggered during their development by binding a lower valency form of self-antigen than is normally required. These findings establish that activation of distinct repertoire-censoring mechanisms depends on quantitative differences in antigen receptor signaling, whose thresholds are determined by negative regulation through PTP1C.