Transitional B Cells Exhibit a B Cell Receptor-Specific Nuclear Defect in Gene Transcription
Transitional B Cells Exhibit a B Cell Receptor-Specific Nuclear Defect in Gene Transcription
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DOI：
10.4049/jimmunol.0802368
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Rawlings, David J.
中科院分区：
文献类型：
--
作者：
Andrews, Sarah F.;Rawlings, David J.
在早期过渡期（T1）B细胞中对BCR参与的负选择的信号程序仍然不清楚。我们对T1与滤泡成熟脾B细胞中的BCR信号传导进行了全面比较。与滤泡成熟B细胞相反，T1不能表达关键的NF-κ B靶基因以响应BCR接合，并且在存活和增殖基因A1和c-Myc的启动子处的活性转录复合物的组装中表现出显著缺陷。令人惊讶的是，与以前的模型相反，经典的蛋白激酶C和I κ B激酶激活，NF-κ B核转位和DNA结合在T1 B细胞中是完整的。此外，尽管NFAT 1表达显著减少，但差异NFAT或AP-1激活不能解释这种转录缺陷。我们的综合研究结果表明，T1 B细胞编程信号和阶段特异性的“核无反应性”后，遇到自我抗原。免疫学杂志，2009，182：2868-2878.
The signaling programs that enforce negative selection in early transitional (T1) B cells in response to BCR engagement remain poorly defined. We conducted a comprehensive comparison of BCR signaling in T1 vs follicular mature splenic B cells. T1, in contrast to follicular mature B cells, failed to express key NF-kappa B target genes in response to BCR engagement and exhibited a striking defect in assembly of an active transcriptional complex at the promoter of the survival and proliferative genes A1 and c-Myc. Surprisingly, and contrary to previous models, classical protein kinase C and I kappa B kinase activation, NF-kappa B nuclear translocation and DNA binding were intact in T1 B cells. Furthermore, despite a marked reduction in NFAT1 expression, differential NFAT or AP-1 activation cannot explain this transcriptional defect. Our combined findings demonstrate that T1 B cells are programmed for signal- and stage-specitic "nuclear nonresponsiveness" upon encounter with self-Ags. The Journal of Immunology, 2009, 182: 2868-2878.