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脐带血B淋巴细胞发生自发凋亡的易感性增加。

Increased susceptibility of cord blood B lymphocytes to undergo spontaneous apoptosis.

作者信息

Kessel A, Yehudai D, Peri R, Pavlotzky E, Bamberger E, Tov N, Toubi E

机构信息

Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Faculty of Medicine Technion, Haifa, Israel.

出版信息

Clin Exp Immunol. 2006 Sep;145(3):563-70. doi: 10.1111/j.1365-2249.2006.03170.x.

Abstract

In this study, we compared the rate of spontaneous apoptosis of B cells from umbilical cord blood with adult B cells and assessed the role of Bcl-2, CD5, interleukin (IL)-4 and B cell-activating factor in B cell spontaneous apoptosis. We found that spontaneous apoptosis of cultured B cells, as assessed by utilizing annexin-V binding, was significantly higher in cord blood than in healthy adult individuals (77.5; 95 CI, 73.5-81.5 versus 59.2; 95 CI, 54-64, respectively, P < 0.0001) and further confirmed by 4' 6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining. Whereas the expression of B cell-activating factor from the tumour necrosis factor family (BAFF) receptor mRNA was similar in B cells from adults and cord blood, we detected lower levels of circulating BAFF in the serum of cord blood (0.68 +/- 0.13 ng versus 1.83 +/- 0.54 ng, P = 0.01). The latter may explain, in part, our observation of lower levels of mean fluorescence intensity of Bcl-2 in cord B cells compared with adults (1.6 +/- 0.9 versus 2.85 +/- 1.3, P = 0.033). CD19(+) CD5(+) B cells from cord blood underwent a lower rate of apoptosis in comparison to CD19(+) CD5(-) B cells (25.1 +/- 9.3%versus 58.5 +/- 12.5%, P < 0.0001). This pattern of sensitivity was comparable in adult blood (15 +/- 5.5%versus 22.7 +/- 9.3%, P = 0.01). Nevertheless, the rate of apoptosis was higher in CD19(+) CD5(+) from cord blood compared to CD19(+) CD5(+) from adults (25.1 +/- 9.3%versus 15 +/- 5.5%, P = 0.0013). The addition of rIL-4 (10 u/ml) to cultured cells decreased B cell apoptosis in a similar fashion in both cord and adults blood. This rescue was strengthened when BAFF (100 microg/ml) was further added. Thus, alterations in Bcl-2 or serum BAFF level may explain the increased rate of cord blood B cell apoptosis.

摘要

在本研究中,我们比较了脐带血B细胞与成人B细胞的自发凋亡率,并评估了Bcl-2、CD5、白细胞介素(IL)-4和B细胞活化因子在B细胞自发凋亡中的作用。我们发现,通过膜联蛋白-V结合评估,培养的B细胞自发凋亡率在脐带血中显著高于健康成人个体(分别为77.5;95%置信区间,73.5 - 81.5与59.2;95%置信区间,54 - 64,P < 0.0001),并通过4',6-二脒基-2-苯基吲哚二盐酸盐(DAPI)染色进一步证实。虽然来自肿瘤坏死因子家族的B细胞活化因子(BAFF)受体mRNA在成人和脐带血B细胞中的表达相似,但我们检测到脐带血血清中循环BAFF水平较低(0.68 ± 0.13 ng对1.83 ± 0.54 ng,P = 0.01)。后者可能部分解释了我们观察到的脐带血B细胞中Bcl-2平均荧光强度水平低于成人(1.6 ± 0.9对2.85 ± 1.3,P = 0.033)。与CD19(+) CD5(-) B细胞相比,脐带血中的CD19(+) CD5(+) B细胞凋亡率较低(25.1 ± 9.3%对58.5 ± 12.5%,P < 0.0001)。这种敏感性模式在成人血液中具有可比性(15 ± 5.5%对22.7 ± 9.3%,P = 0.01)。然而,脐带血中CD19(+) CD5(+)的凋亡率高于成人中的CD19(+) CD5(+)(25.1 ± 9.3%对15 ± 5.5%,P = 0.0013)。向培养细胞中添加重组IL-4(10 U/ml)以类似方式降低了脐带血和成人血液中的B细胞凋亡。当进一步添加BAFF(100 μg/ml)时,这种挽救作用得到增强。因此,Bcl-2或血清BAFF水平的改变可能解释了脐带血B细胞凋亡率的增加。

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本文引用的文献

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Transplantation. 2005 Feb 15;79(3 Suppl):S4-7. doi: 10.1097/01.tp.0000153289.42663.ae.

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