抗原刺激导致BCR膜免疫球蛋白与Ig-α/Ig-β解离：对受体脱敏的影响
Antigen-stimulated dissociation of BCR mIg from Ig-alpha/Ig-beta: implications for receptor desensitization.
作者信息
Vilen B J, Nakamura T, Cambier J C
机构信息
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
出版信息
Immunity. 1999 Feb;10(2):239-48. doi: 10.1016/s1074-7613(00)80024-2.
Abstract
B cell antigen receptor (BCR) ligation leads to receptor desensitization wherein BCR remain competent to bind antigen and yet fail to transduce signals. Desensitized BCR exhibit a defect at the most proximal level of signal transduction, consistent with failed transmission of signals through the receptor complex. We report that antigen stimulation leads to dissociation or destabilization of the BCR reflected by inability to coimmunoprecipitate Ig-alpha/Ig-beta with mIg. This destabilization is temporally correlated with desensitization and occurs in BCR containing mIgM and mIgD. Induction of BCR destabilization requires tyrosine kinase activation but is not induced by phosphatase inhibitors. BCR destabilization occurs at the cell surface and "dissociated" Ig-alpha/Ig-beta complexes remain responsive to anti-Ig-beta stimulation, suggesting that mIg-transducer uncoupling may mediate receptor desensitization.
摘要
B细胞抗原受体（BCR）连接导致受体脱敏，即BCR仍有能力结合抗原，但无法转导信号。脱敏的BCR在信号转导的最近端水平表现出缺陷，这与通过受体复合物的信号传递失败一致。我们报告抗原刺激导致BCR的解离或不稳定，表现为无法用mIg进行共免疫沉淀Ig-α/Ig-β。这种不稳定在时间上与脱敏相关，并且发生在含有mIgM和mIgD的BCR中。BCR不稳定的诱导需要酪氨酸激酶激活，但不受磷酸酶抑制剂诱导。BCR不稳定发生在细胞表面，“解离的”Ig-α/Ig-β复合物仍对抗Ig-β刺激有反应，这表明mIg-转导子解偶联可能介导受体脱敏。
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本文引用的文献
1
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Immunity. 1998 Aug;9(2):239-46. doi: 10.1016/s1074-7613(00)80606-8.
2
Membrane compartmentation is required for efficient T cell activation.有效的T细胞激活需要膜区室化。
Immunity. 1998 Jun;8(6):723-32. doi: 10.1016/s1074-7613(00)80577-4.
3
CD79 alpha/CD79 beta heterodimers are expressed on pro-B cell surfaces without associated mu heavy chain.CD79α/CD79β异二聚体在原B细胞表面表达，且不与μ重链相关联。
Int Immunol. 1997 Nov;9(11):1767-72. doi: 10.1093/intimm/9.11.1767.
4
5
The complexity of signaling pathways activated by the BCR.由BCR激活的信号通路的复杂性。
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Molecular mechanisms in B cell antigen receptor signaling.B细胞抗原受体信号传导的分子机制。
Curr Opin Immunol. 1997 Jun;9(3):309-18. doi: 10.1016/s0952-7915(97)80075-1.
7
B cell antigen receptor desensitization: disruption of receptor coupling to tyrosine kinase activation.B细胞抗原受体脱敏：受体与酪氨酸激酶激活偶联的破坏。
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8
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