Hayakawa Kyoko, Formica Anthony M, Colombo Matthew J, Ichikawa Daiju, Shinton Susan A, Brill-Dashoff Joni, Hardy Richard R
Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Keio University Faculty of Pharmacy, Juntendo University School of Medicine, Tokyo, Japan.
Ann N Y Acad Sci. 2015 Dec;1362:250-5. doi: 10.1111/nyas.12768. Epub 2015 Apr 23.
B cells generated early during fetal/neonatal B-1 development in mice include autoreactive cells with detectable CD5 upregulation induced by B cell receptor (BCR) signaling (B1a cells). A fraction of B1a cells are maintained by self-renewal for life, with the potential risk of dysregulated growth and progression to chronic lymphocytic leukemia (CLL)/lymphoma during aging. In studies using the Eμ-hTCL1 transgenic mouse system, it became clear that this B1a subset has a higher potential than other B cell subsets for progression to CLL. We have generated several autoreactive germline BCR gene models to compare B cells generated under conditions of natural exposure to autoantigen. Analysis of the mice has been key in understanding the importance of the BCR and BCR signaling for generating different B cell subsets and for investigating the cellular origin of B-CLL.
在小鼠胎儿/新生儿B-1细胞发育早期产生的B细胞包括自身反应性细胞，这些细胞可检测到由B细胞受体（BCR）信号诱导的CD5上调（B1a细胞）。一部分B1a细胞通过自我更新维持终生，在衰老过程中存在生长失调和发展为慢性淋巴细胞白血病（CLL）/淋巴瘤的潜在风险。在使用Eμ-hTCL1转基因小鼠系统的研究中，很明显这个B1a亚群比其他B细胞亚群更易发展为CLL。我们已经构建了几个自身反应性种系BCR基因模型，以比较在自然暴露于自身抗原条件下产生的B细胞。对这些小鼠的分析对于理解BCR和BCR信号在产生不同B细胞亚群中的重要性以及研究B-CLL的细胞起源至关重要。
