Immunoglobulin μ Heavy Chains Do Not Mediate Tyrosine Phosphorylation of Igα from the ER-cis-Golgi 1
Immunoglobulin μ Heavy Chains Do Not Mediate Tyrosine Phosphorylation of Igα from the ER-cis-Golgi 1
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免疫球蛋白 μ 重链不介导 ER-cis-Golgi 1 中 Igα 的酪氨酸磷酸化
DOI：
10.4049/jimmunol.171.6.3091
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
H. Jäck
中科院分区：
文献类型：
--
作者：
D. Mielenz;Anja Ruschel;Christian Vettermann;H. Jäck
Ig受体传递的信号指导功能性B淋巴细胞的发育。例如，早期μ重链（μ hc）阳性的前b细胞的克隆扩增需要一个由μ重链、替代L链和信号二聚体Igαβ组成的信号受体复合物（pre-BCR）的组装。然而，只有一小部分bcr前体被转运到细胞表面，这表明bcr前体信号传导已经从细胞内腔室（如内质网）启动。在替代L链缺陷小鼠中，前b细胞的分化和IgH位点等位基因的排除进一步支持μ hc介导的细胞内信号通路的存在。为了确定信号敏感的Ig复合物是否已经在内质网中组装，我们分析了在J558L浆细胞瘤和38B9前b细胞中，通过转运敏感的IgL链配对或ER保留的非配对μHC转染后，过氧化物酸盐对Igα酪氨酸磷酸化的影响。流式细胞术、Western blot- immunodeposition -kinase联合检测和共聚焦显微镜显示非配对和配对μHC均与igg αβ二聚体组装；然而，与配对μHC相比，非配对μHC保留在er顺式-高尔基室中，并且在pervanadate处理细胞后既不与src激酶lyn共定位，也不诱导Igα的酪氨酸磷酸化。基于这些发现，我们提出了一个由μHC、Igαβ和相关激酶组成的信号敏感的Ig复合物在er后室中组装，从而支持了前bcr必须被运输到细胞表面以启动前bcr信号传导的观点。
Signals delivered by Ig receptors guide the development of functional B lymphocytes. For example, clonal expansion of early μ heavy chain (μHC)-positive pre-B cells requires the assembly of a signal-competent pre-B cell receptor complex (pre-BCR) consisting of a μHC, a surrogate L chain, and the signal dimer Igαβ. However, only a small fraction of the pre-BCR is transported to the cell surface, suggesting that pre-BCR signaling initiates already from an intracellular compartment, e.g., the endoplasmic reticulum (ER). The finding that differentiation of pre-B cells and allelic exclusion at the IgH locus take place in surrogate L chain-deficient mice further supports the presence of a μHC-mediated intracellular signal pathway. To determine whether a signal-competent Ig complex can already be assembled in the ER, we analyzed the consequence of pervanadate on tyrosine phosphorylation of Igα in J558L plasmacytoma and 38B9 pre-B cells transfected with either a transport-competent IgL chain-pairing or an ER-retained nonpairing μHC. Flow cytometry, combined Western blot-immunoprecipitation-kinase assays, and confocal microscopy revealed that both the nonpairing and pairing μHC assembled with the Igαβ dimer; however, in contrast to a pairing μHC, the nonpairing μHC was retained in the ER-cis-Golgi compartment, and neither colocalized with the src kinase lyn nor induced tyrosine phosphorylation of Igα after pervanadate treatment of cells. On the basis of these findings, we propose that a signal-competent Ig complex consisting of μHC, Igαβ, and associated kinases is assembled in a post-ER compartment, thereby supporting the idea that a pre-BCR must be transported to the cell surface to initiate pre-BCR signaling.
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影响因子：
32.4
作者：
GRAWUNDER, U;LEU, TMJ;WINKLER, TH
通讯作者：
WINKLER, TH
另一种莫特细胞。
DOI：
10.1073/pnas.89.24.11688
发表时间：
1992
影响因子：
11.1
作者：
Jäck,HM;Beck-Engeser,G;Sloan,B;Wong,ML;Wabl,M
通讯作者：
Wabl,M
影响因子：
4.4
作者：
Martin, F;Chen, XJ;Kearney, JF
通讯作者：
Kearney, JF
DOI：
10.1073/pnas.88.14.6284
发表时间：
1991-07
影响因子：
11.1
作者：
N. Nishimoto;H. Kubagawa;T. Ohno;G. Gartland;A. Stanković;Max D. CooPE
通讯作者：
N. Nishimoto;H. Kubagawa;T. Ohno;G. Gartland;A. Stanković;Max D. CooPE
Ig 重链 V 区的替代轻链依赖性选择。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Keyna,U;Beck-Engeser,GB;Jongstra,J;Applequist,SE;Jack,HM
通讯作者：
Jack,HM