Entry of B cell receptor into signaling domains is inhibited in tolerant B cells.
Entry of B cell receptor into signaling domains is inhibited in tolerant B cells.
复制标题
B细胞受体进入信号传导结构域被抑制在耐受的B细胞中。
DOI：
10.1084/jem.191.8.1443
复制
发表时间：
2000-04-17
影响因子：
15.3
通讯作者：
Goodnow, C C
中科院分区：
文献类型：
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作者：
Weintraub, B C;Jun, J E;Bishop, A C;Shokat, K M;Thomas, M L;Goodnow, C C
在表达识别自身抗原的受体的 B 细胞中，通过 B 细胞抗原受体 (BCR) 的信号转导发生了改变。为了了解自身反应性 B 细胞信号传导变化的分子基础，使用转基因模型分离出同质的耐受 B 淋巴细胞群体。将这些细胞与类似的初始 B 淋巴细胞群进行比较。我们发现，在抗原结合后 6 秒内，来自初始 B 细胞的 BCR 进入细胞的去污剂不溶性结构域，然后 BCR 磷酸化可检测到增加。该部分似乎对信号传导很重要，因为它富含 lyn 激酶，但缺乏 CD45 酪氨酸磷酸酶，而且进入该结构域的 BCR 变得更加高度磷酸化。 BCR 分配到该部分不受 src 家族激酶抑制的影响。耐受性 B 细胞不能有效地将 BCR 分配到去污剂不溶性结构域中，这为它们响应抗原时酪氨酸激酶激活和钙通量减少提供了解释。这些结果确定了抗原受体信号传导和自我耐受的早期调控步骤。
Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium flux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.