Impaired T- and B-cell development in Tcl1-deficient mice
Impaired T- and B-cell development in Tcl1-deficient mice
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DOI：
10.1182/blood-2004-04-1453
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Russo, G
中科院分区：
文献类型：
--
作者：
Kang, SM;Narducci, MG;Russo, G
TCl 1，其过表达可导致T细胞白血病，通常在早期胚胎组织、卵巢和淋巴系细胞中表达。我们对小鼠B系细胞的分析表明，Tcl 1表达起始于前B细胞，并持续存在于脾边缘区和滤泡B细胞。T细胞系Tcl 1的表达开始于胸腺祖细胞，在CD4（+）CD8（+）胸腺细胞中持续，并在成熟T细胞中消失。在Tcl 1基因缺陷小鼠中，我们发现B淋巴细胞生成在前B细胞阶段受到损害，T细胞淋巴细胞生成在CD4（+）CD8（+）胸腺细胞阶段受到损害。胸腺细胞对抗CD3 ε诱导的细胞凋亡的敏感性也相应增加。脾滤泡和生发中心B细胞数量减少，伴有免疫球蛋白G1（IgG 1）和IgG 2 B抗体在反应细胞中的产生受损。在Tcl 1缺陷小鼠中，我们发现B淋巴细胞生成在前B细胞阶段受到损害，T细胞淋巴细胞生成在CD4（+）CD8（+）胸腺细胞阶段受到损害。胸腺细胞对抗CD3 ε诱导的细胞凋亡的敏感性也相应增加。脾滤泡和生发中心B细胞数量减少，伴随免疫球蛋白G1（IgG1）和IgG2 B抗体响应T依赖性抗原的产生受损。Tcl 1（-/-）小鼠的边缘区B细胞和T细胞非依赖性抗体应答也减少。该分析表明，Tcl 1（Akt信号传导的共激活剂）在正常T细胞和B细胞发育和功能中具有重要作用。
TCl1, the overexpression of which may result in T-cell leukemia, is normally expressed in early embryonic tissues, the ovary, and lymphoid lineage cells. Our analysis of mouse B-lineage cells indicates that Tcl1 expression is initiated in pro-B cells and persists in splenic marginal zone and follicular B cells. T-lineage Tcl1 expression begins in thymocyte progenitors, continues in CD4(+)CD8(+) thymocytes, and is extinguished in mature T cells. In Tcl1-cleficient mice, we found B lymphopoiesis to be compromised at the pre-B cell stage and T-cell lymphopoiesis to be impaired at the CD4(+)CD8(+) thymocyte stage. A corresponding increase was observed in thymocyte susceptibility to anti-CD3epsilon-induced apoptosis. Reduced numbers of splenic follicular and germinal center B cells were accompanied by impaired production of immunoglobulin G1 (IgG1) and IgG2b antibodies in response cells. In Tcl1-deficient mice, we found B lymphopoiesis to be compromised at the pre-B cell stage and T-cell lymphopoiesis to be impaired at the CD4(+)CD8(+) thymocyte stage. A corresponding increase was observed in thymocyte susceptibility to anti-CD3epsilon-induced apoptosis. Reduced numbers of splenic follicular and germinal center B cells were accompanied by impaired production of immunoglobulin G1 (IgG1) and IgG2b antibodies in response to a T-dependent antigen. The marginal zone B cells and T-cell-independent antibody responses were also diminished in Tcl1(-/-)mice. This analysis indicates a significant role for Tcl1, a coactivator of Akt signaling, in normal T- and B-cell development and function.