XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development.
XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development.
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DOI：
10.1084/jem.20090738
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发表时间：
2009-09-28
期刊：
影响因子：
--
通讯作者：
Glimcher LH
中科院分区：
文献类型：
--
作者：
Todd DJ;McHeyzer-Williams LJ;Kowal C;Lee AH;Volpe BT;Diamond B;McHeyzer-Williams MG;Glimcher LH
未折叠蛋白反应（UPR）是一种应激反应通路，由浆细胞等高度分泌细胞的内质网中未折叠蛋白负荷增加所驱动。X盒结合蛋白1（XBP1）是一种转录因子，介导UPR的一个分支，对分泌抗体的浆细胞的发育至关重要。然而，浆细胞只是终末分化B细胞的一类，对于XBP1在另一类细胞——记忆B细胞中的作用知之甚少。我们构建了一种XBP1^{fl/fl} CD19^{+/cre}条件性敲除（XBP1^{CD19}）小鼠，以基于我们目前对XBP1在浆细胞分化中的功能的理解，并探索XBP1在记忆细胞发育中的作用。利用该模型，我们表明在一种自身抗体介导的小鼠狼疮模型中，XBP1^{CD19}小鼠可免受疾病影响。我们还确定了一个新的发育阶段，在该阶段B细胞表达传统的浆细胞标志物CD138（多配体聚糖 - 1），但尚未经历依赖于XBP1的功能和形态分化成为分泌抗体的细胞。最后，我们表明在XBP1^{CD19}小鼠中记忆B细胞发育正常，这表明XBP1介导的功能独立于任何记忆细胞谱系定型而发生。
The unfolded protein response (UPR) is a stress response pathway that is driven by the increased load of unfolded proteins in the endoplasmic reticulum of highly secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development of antibody-secreting PCs. PCs represent only one class of terminally differentiated B cells, however, and little is known about the role for XBP1 in the other class: memory B cells. We have developed an XBP1fl/fl CD19+/cre conditional knockout (XBP1CD19) mouse to build upon our current understanding of the function of XBP1 in PC differentiation as well as to explore the role of XBP1 in memory cell development. Using this model, we show that XBP1CD19 mice are protected from disease in an autoantibody-mediated mouse lupus model. We also identify a novel developmental stage at which B cells express the traditional PC marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and morphological differentiation into antibody-secreting cells. Finally, we show that memory B cells develop normally in XBP1CD19 mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment.
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影响因子：
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