Katsumata M, Siegel R M, Louie D C, Miyashita T, Tsujimoto Y, Nowell P C, Greene M I, Reed J C
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11376-80. doi: 10.1073/pnas.89.23.11376.
We have produced bcl-2 transgenic mice by using a construct which mimics the t(14;18) translocation in human follicular lymphomas. Although lymphoid tissues from all transgenic mice contained high levels of human Bcl-2 protein, transgene expression was differentially regulated within the B- and T-cell compartments of lines derived from various founder mice. We have characterized the phenotypes of two lines of bcl-2 transgenic mice (line 2 and line 6) in which bcl-2 transgene expression was restricted primarily to the T- or B-cell lineages, respectively. Analysis of line 6 lymphocytes revealed a polyclonal expansion of B cells, and these B cells exhibited prolonged survival in vitro. In line 2 mice, numbers of T cells in the peripheral lymphoid tissues were more moderately elevated despite enhanced T-cell survival in vitro. Line 2 transgenic mice also showed significantly increased proportions of thymocytes with a mature phenotype. Taken together, these findings suggest different roles for bcl-2 in the in vivo regulation of B- and T-cell development and homeostasis.
我们通过使用一种模拟人类滤泡性淋巴瘤中t(14;18)易位的构建体，培育出了bcl-2转基因小鼠。尽管所有转基因小鼠的淋巴组织都含有高水平的人Bcl-2蛋白，但来自不同奠基小鼠品系的B细胞和T细胞区室中转基因的表达受到不同的调控。我们已经对两系bcl-2转基因小鼠（2系和6系）的表型进行了表征，其中bcl-2转基因的表达分别主要局限于T细胞或B细胞谱系。对6系淋巴细胞的分析显示B细胞出现多克隆扩增，并且这些B细胞在体外表现出延长的存活时间。在2系小鼠中，尽管体外T细胞存活增强，但外周淋巴组织中T细胞的数量只是适度增加。2系转基因小鼠还显示出具有成熟表型的胸腺细胞比例显著增加。综上所述，这些发现表明bcl-2在体内B细胞和T细胞发育及稳态调控中具有不同作用。
