Biogenesis of secretory organelles during B cell differentiation
Biogenesis of secretory organelles during B cell differentiation
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DOI：
10.1189/jlb.1208774
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发表时间：
2010-02-01
影响因子：
5.5
通讯作者：
Ward, Theresa H.
中科院分区：
文献类型：
--
作者：
Kirk, Semra J.;Cliff, Jacqueline M.;Ward, Theresa H.
B细胞分化为分泌igg的浆细胞需要分泌细胞器的扩张来应对增加的负载。为了评估这一过程的时间表，我们量化了分泌细胞器相对于Ig分泌的扩张动力学，并检测了体外激活人B淋巴细胞后分泌运输的调节成分。未受刺激的B细胞含有极少的内膜。激活后，内质网膜诱导表现为直径0.5-1 μ m的紧密排列的球形结构，集中在核旁位置。当细胞分化为浆母细胞时，细胞大小急剧增大，但内质网仍然集中在细胞核附近，直到后来才充满整个细胞。与此形成鲜明对比的是，先前在其他细胞类型中的研究发现，在间期，内质网随着细胞大小的增加而同步扩张，这是通过内质网小管在PM下的延伸而实现的。在这项研究中，高尔基体始终保持单一的核旁结构，但在B细胞激活过程中，其体积线性扩大六倍。此外，随着细胞的活跃增殖，内质网出口位点迅速增殖，数量几乎增加了四倍，与此同时，Ig分泌也急剧增加。这些发现表明，在原代人B细胞中，细胞器生物发生和扩增的控制受到Ig合成引起的货物通量的不同调节。j . Leukoc。生物学报87:245-255；2010.
The differentiation of B cells into Ig-secreting plasma cells requires the expansion of secretory organelles to cope with the increased cargo load. To evaluate the timeline of this process, we have quantitated the kinetics of secretory organelle expansion relative to Ig secretion and examined regulatory components of secretory transport following in vitro activation of human B lymphocytes. Unstimulated B cells contain minimal endomembranes. After activation, ER membrane induction appears as tightly packed spherical structures of 0.5-1 mu m diameter concentrated in a juxtanuclear position. When the cells differentiate into plasmablasts, there is dramatic cell-size increase, but the ER remains concentrated close to the nucleus and only later fills the entire cell. In sharp contrast, previous studies in other cell types have found that the ER expands in synchrony with increasing cell size during interphase, by extension of ER tubules under the PM. In this study, the Golgi remains consistently as a single juxtanuclear structure but linearly expands sixfold in volume during B cell activation. Furthermore, following active cell proliferation, ER exit sites proliferate rapidly, increasing almost fourfold in number, in parallel with a sharp increase in Ig secretion. These findings demonstrate that the control of organelle biogenesis and expansion in primary human B cells are differentially regulated by cargo flux caused by Ig synthesis. J. Leukoc. Biol. 87: 245-255; 2010.