Holmes Melissa L, Pridans Clare, Nutt Stephen L
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Immunol Cell Biol. 2008 Jan;86(1):47-53. doi: 10.1038/sj.icb.7100134. Epub 2007 Nov 13.
The activity of the transcription factor paired box gene 5 (Pax5) is essential for many aspects of B lymphopoiesis including the initial commitment to the lineage, immunoglobulin rearrangement, pre-B cell receptor signalling and maintaining cell identity in mature B cells. Deregulated or reduced Pax5 activity has also been implicated in B-cell malignancies both in human disease and mouse models. Candidate gene approaches and biochemical analysis have revealed that Pax5 regulates B lymphopoiesis by concurrently activating B cell-specific gene expression as well as repressing the expression of genes, many of which are associated with non-B cell lineages. These studies have been recently complemented with more exhaustive microarray studies, which have identified and validated a large panel of Pax5 target genes. These target genes reveal a gene regulatory network, with Pax5 at its centre that controls the B-cell gene expression programme.
转录因子配对盒基因5(Pax5)的活性对于B淋巴细胞生成的许多方面至关重要,包括对该谱系的初始定向、免疫球蛋白重排、前B细胞受体信号传导以及维持成熟B细胞中的细胞特性。在人类疾病和小鼠模型中,Pax5活性失调或降低也与B细胞恶性肿瘤有关。候选基因方法和生化分析表明,Pax5通过同时激活B细胞特异性基因表达以及抑制许多与非B细胞谱系相关的基因表达来调节B淋巴细胞生成。最近,这些研究得到了更详尽的微阵列研究的补充,这些研究鉴定并验证了大量Pax5靶基因。这些靶基因揭示了一个以Pax5为中心的基因调控网络,该网络控制着B细胞基因表达程序。