Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling.

Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling.
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CD22的唾液酸结合结构域是B细胞受体信号传导负调控所必需的。

DOI:
10.1084/jem.20011796
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发表时间:
2002-05-06
影响因子:
15.3
通讯作者:
Wortis, Henry H
Wortis, Henry H
中科院分区:
医学1区
文献类型:
--
作者:
Jin, Lei;McLean, Paul A;Neel, Benjamin G;Wortis, Henry H

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CD22是B细胞抗原受体信号传导的负调节因子,与终止于α 2,6唾液酸的糖缀合物结合。CD22的生理配体尚不清楚。我们想知道唾液酸结合结构域是否是CD22作为负调节因子所必需的。我们产生了两个缺乏唾液酸结合活性的突变体,并在一种新的CD22 - / -小鼠B细胞系中表达它们。表达CD22突变体的抗igm激活的B细胞比表达野生型CD22的细胞有更大的Ca2+反应。每个变体也减少了CD22酪氨酸磷酸化和Src同源2结构域蛋白酪氨酸磷酸酶-1的关联。这些数据表明,CD22的α 2,6唾液酸配体结合活性对其负调控功能至关重要。
CD22, a negative regulator of B cell antigen receptor signaling, binds glycoconjugates terminating in α2, 6 sialic acid. The physiological ligand(s) for CD22 remain unknown. We asked whether the sialic acid binding domains are necessary for CD22 to function as a negative regulator. We generated two mutants that lack sialic acid binding activity and expressed them in a novel CD22−/− murine B cell line. Anti-IgM activated B cells expressing either CD22 mutant had greater Ca2+ responses than cells expressing wild-type CD22. Each variant also had reduced CD22 tyrosine phosphorylation and Src homology 2 domain–containing protein tyrosine phosphatase-1 association. These data suggest that the α2, 6 sialic acid ligand binding activity of CD22 is critical for its negative regulatory functions.