Lipid rafts associate with intracellular B cell receptors and exhibit a B cell stage-specific protein composition

Lipid rafts associate with intracellular B cell receptors and exhibit a B cell stage-specific protein composition
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DOI:
10.4049/jimmunol.174.6.3508
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发表时间:
2005-03-15
影响因子:
4.4
通讯作者:
Jäck, HM
Jäck, HM
中科院分区:
医学2区
文献类型:
--
作者:
Mielenz, D;Vettermann, C;Jäck, HM

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脂筏是BCR信号转导的平台。为了更好地定义这些膜微区的分子基础,我们使用二维凝胶电泳和质谱来表征来自成熟和未成熟B细胞系的脂筏蛋白。在51种特定的筏蛋白中,我们通过肽质量指纹图谱鉴定了18种蛋白。其中,我们发现液泡ATP酶亚基α-1和β-2,波形蛋白,γ-肌动蛋白,丝裂素,和抑制素。这些以前都没有报道过在脂筏的B细胞。差异筏协会的三种蛋白质,包括一种新的潜在的信号分子swiprosin-1,与特定阶段的敏感性B细胞BCR诱导的细胞凋亡。此外,在成熟的脂筏中检测到MHC II类分子,但未成熟的B细胞。这一有趣的发现指出了脂筏在B细胞成熟过程中调节Ag呈递的作用。最后,B细胞系CH 27中的一部分BCR组成性地存在于脂筏中。令人惊讶的是,该部分既不在细胞表面表达,也不完全O-糖基化。因此,我们得出结论,分区的BCR到脂筏发生在内质网/顺式高尔基体室,并可能代表一个控制机制的表面运输。
Lipid rafts serve as platforms for BCR signal transduction. To better define the molecular basis of these membrane microdomains, we used two-dimensional gel electrophoresis and mass spectrometry to characterize lipid raft proteins from mature as well as immature B cell lines. Of 51 specific raft proteins, we identified a total of 18 proteins by peptide mass fingerprinting. Among them, we found vacuolar ATPase subunits alpha-1 and beta-2, vimentin, gamma-actin, mitofilin, and prohibitin. None of these has previously been reported in lipid rafts of B cells. The differential raft association of three proteins, including a novel potential signaling molecule designated swiprosin-1, correlated with the stage-specific sensitivity of B cells to BCR-induced apoptosis. In addition, MHC class II molecules were detected in lipid rafts of mature, but not immature B cells. This intriguing finding points to a role for lipid rafts in regulating Ag presentation during B cell maturation. Finally, a fraction of the BCR in the B cell line CH27 was constitutively present in lipid rafts. Surprisingly, this fraction was neither expressed at the cell surface nor fully O-glycosylated. Thus, we conclude that partitioning the BCR into lipid rafts occurs in the endoplasmic reticulum/cis-Golgi compartment and may represent a control mechanism for surface transport.