DIFFERENTIAL SIGNALING THROUGH THE IG-ALPHA AND IG-BETA COMPONENTS OF THE B-CELL ANTIGEN RECEPTOR

DIFFERENTIAL SIGNALING THROUGH THE IG-ALPHA AND IG-BETA COMPONENTS OF THE B-CELL ANTIGEN RECEPTOR
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DOI:
10.1002/eji.1830230422
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发表时间:
1993-04-01
影响因子:
5.4
通讯作者:
RETH, M
RETH, M
中科院分区:
医学3区
文献类型:
--
作者:
KIM, KM;ALBER, G;RETH, M

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B 细胞抗原受体是包含抗原结合免疫球蛋白分子和 Ig-α/Ig-β 异二聚体的复合物,其可能将 B 细胞抗原受体与细胞内信号传导成分连接起来。分析 B 细胞抗原受体胞质部分的功能特性。我们使用K46 B淋巴瘤系(IgG2a,chi)来表达由CD8α分子的细胞外和跨膜部分以及Ig-α(CD8α/Ig-α)、Ig-β(CD8α/Ig-β)蛋白或膜结合的γ2a重链(CD8α/γ2a)的细胞质序列组成的嵌合分子。在这三种类型的嵌合分子中,只有CD8α/Ig-α和CD8α/Ig-β能够转导信号,而CD8α/gamma2a则不能。从而提供了Ig-α和Ig-β的细胞质尾部具有信号传导能力的第一个证据。与抗 CD8α 抗体交联后,两种分子均诱导细胞内游离钙离子和 MAP 激酶磷酸化类似的增加。然而,蛋白酪氨酸激酶。通过 CD8α/Ig-α 强烈激活,仅通过 CD8α/Ig-β 分子轻微激活。这表明 Ig-α 和 Ig-β 蛋白在通过 B 细胞抗原受体的信号转导过程中具有不同的作用。
The B cell antigen receptor is a complex containing the antigen-binding immunoglobulin molecules and the Ig-alpha/Ig-beta heterodimer which presumably connects the B cell antigen receptor to intracellular signaling components. To analyze the functional properties of the cytoplasmic parts of the B cell antigen receptor. we used the K46 B lymphoma line (IgG2a, chi) to express chimeric molecules composed of the extracellular and transmembrane part of the CD8alpha molecule and the cytoplasmic sequence of either the Ig-alpha (CD8alpha/Ig-alpha), the Ig-beta (CD8alpha/Ig-beta) protein or the membrane-bound gamma2a heavy chain (CD8alpha/gamma2a). From these three types of chimeric molecules only CD8alpha/Ig-alpha and CD8alpha/Ig-beta, but not CD8alpha/gamma2a, could transduce signals. thus providing the first evidence that the cytoplasmic tail of Ig-alpha and Ig-beta have a signaling capacity. After cross-linking with anti-CD8alpha antibodies, both molecules induced a similar increase in intracellular free calcium ion and in MAP kinase phosphorylation. Protein tyrosine kinases, however. were strongly activated via the CD8alpha/Ig-alpha and only marginally via the CD8alpha/Ig-beta molecule. This suggests that the Ig-alpha and Ig-beta proteins have distinct roles during signal transduction through the B cell antigen receptor.