Different kinetics of Blimp-1 induction in B cell subsets revealed by reporter gene
Different kinetics of Blimp-1 induction in B cell subsets revealed by reporter gene
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DOI：
10.4049/jimmunol.178.7.4104
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发表时间：
2007-04-01
影响因子：
4.4
通讯作者：
Tarlinton, David M.
中科院分区：
文献类型：
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作者：
Fairfax, Kirsten A.;Corcoran, Lynn M.;Tarlinton, David M.
转录抑制因子Blimp-1（B淋巴细胞诱导的成熟蛋白1）已被描述为B细胞分化为Ab分泌细胞（ASC）的“主调节因子”。尽管有越来越多的证据表明Blimp-1在浆细胞发育中的重要性和必要性，但关于它在B细胞亚群的B细胞分化中所起的作用以及它在ASC分化期间与其他转录因子如Pax 5和Bcl 6相互作用的方式还不确定。使用在Blimp-1调节元件（Blimp-1（GFP/+））控制下表达GFP的小鼠，我们检查了活化后纯化的B细胞亚群中Blimp-1上调的动力学。B1细胞显示Blimp-1对所测试的促分裂剂的响应最快速和显著的上调，其次是边缘区B细胞，然后是常规B2细胞。有趣的是，只有III细胞响应于CpG而显著上调Blimp-1表达。B1细胞在分离时分泌可忽略的IG，但能够上调Blimp-1并在刺激后28小时内启动IG分泌。同样令人感兴趣的是，B1细胞具有介于幼稚B细胞和ASC之间的转录因子谱，表明B1细胞处于半活化状态。转移的初始Blimp-1（GFP/+）B1和B2细胞均在骨髓中产生ASC，表明BI细胞进入长寿命ASC区室没有内在屏障。
The transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein 1) has been described as a "master regulator" of B cell differentiation into Ab-secreting cells (ASCs). Although there is mounting evidence for the importance and necessity of Blimp-1 in plasma cell development, there is uncertainty as to the role it plays in B cell differentiation of B cell subsets and the way in which it may interact with other transcription factors such as Pax5 and Bcl6 during ASC differentiation. Using a mouse expressing GFP under the control of the Blimp-1 regulatory elements (Blimp-1(GFP/+)), we examined the kinetics of Blimp-1 up-regulation in purified B cell subsets following activation. B1 cells showed the most rapid and pronounced up-regulation of Blimp-1 in response to the mitogens tested, followed by marginal zone B cells and then conventional B2 cells. Interestingly, only Ill cells substantially up-regulated Blimp-1 expression in response to CpG. B1 cells secreted negligible Ig upon isolation but were able to up-regulate Blimp-1 and initiate Ig secretion within 28 h of stimulation. Also of interest, B1 cells have a transcriptional factor profile that is intermediate between a naive B cell and an ASC, indicative of the semiactivated state of B1 cells. Transferred naive Blimp-1(GFP/+) B1 and B2 cells both gave rise to ASCs in the bone marrow, suggesting no intrinsic barriers to BI cell entry into the long-lived ASC compartment.