Plasma cell differentiation requires the transcription factor XBP-1
Plasma cell differentiation requires the transcription factor XBP-1
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DOI：
10.1038/35085509
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发表时间：
2001-07-19
期刊：
影响因子：
64.8
通讯作者：
Glimcher, LH
中科院分区：
文献类型：
--
作者：
Reimold, AM;Iwakoshi, NN;Glimcher, LH
在确定参与b淋巴细胞谱系早期规范的转录因子方面取得了相当大的进展。然而，对于控制成熟活化B细胞向抗体分泌浆细胞转变的因素知之甚少。在这里，我们报道了转录因子XBP-1是产生浆细胞所必需的。XBP-1转录本在体外通过刺激诱导浆细胞分化迅速上调，并在类风湿滑膜浆细胞中发现高水平。当引入b系细胞时，XBP-1启动浆细胞分化。缺乏XBP-1的小鼠淋巴嵌合体具有正常数量的活化B淋巴细胞增殖，分泌细胞因子并形成正常的生发中心。然而，它们分泌的任何同型免疫球蛋白都非常少，而且由于浆细胞明显缺失，它们无法控制b细胞依赖性多瘤病毒的感染。XBP-1是唯一已知的B淋巴细胞向浆细胞最终分化选择性和特异性所需的转录因子。
Considerable progress has been made in identifying the transcription factors involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activated B cells to antibody-secreting plasma cells. Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres. However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells.