Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras.

Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras.
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人源 IgG 水平作为 Hu-PBL/SCID 嵌合体中 EBV 相关淋巴瘤模型的指标

DOI:
10.1186/1743-422x-8-213
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发表时间:
2011-05-09
期刊:
影响因子:
4.8
通讯作者:
Gan R
Gan R
中科院分区:
医学3区
文献类型:
--
作者:
Tang Y;He R;Zhang Y;Liu F;Cheng A;Wu Y;Gan R

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爱泼斯坦-巴尔病毒(Epstein-Barr Virus,EBV)与多种类型的人类淋巴瘤密切相关。动物模型对于阐明人类EBV相关淋巴瘤的发病机制至关重要。本研究旨在探讨人免疫球蛋白G水平与人EB病毒相关性淋巴瘤发生的关系。方法将EBV阳性供者的人外周血淋巴细胞接种到SCID小鼠体内。免疫组织化学染色检测肿瘤细胞分化抗原。用原位杂交法检测诱导肿瘤组织中EB病毒的感染情况。采用单向免疫扩散法检测12只SCID小鼠血清中的免疫球蛋白G浓度。免疫组织化学染色显示,所有诱导肿瘤均为LCA阳性,B细胞标志物(CD20、CD79a)阳性,T细胞标志物(CD3、CD45RO)阴性。根据这些形态和免疫组织化学特征,可以诊断为人类B细胞淋巴瘤。原位杂交显示肿瘤细胞有EBV编码的小RNA-1(EBER-1)。移植后第15天,SCID小鼠血清中可检测到人源性免疫球蛋白G,其中6例HU-PBL/SCID嵌合体的免疫球蛋白水平随着肿瘤的发展而升高。结论EBV+供者的人外周血淋巴细胞移植到SCID小鼠体内后,小鼠血清和B细胞淋巴瘤中的人免疫球蛋白水平升高。我们的研究结果表明,从Hu-PBL/SCID小鼠的外周血中不断增加的人源性免疫球蛋白可用于监测EB病毒相关的人B细胞淋巴瘤在实验动物中的发展。
BackgroundEpstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. The aim of the present study is to evaluate the association between human IgG concentration and EBV-associated lymphoma development in huPBL/SCID mice.MethodsHuman peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were inoculated intraperitoneally into SCID mouse. Immunohistochemical staining was used to examine differentiated antigens of tumor cells. EBV infection of the induced tumors was detected byin situhybridization. IgG concentrations in the serums of 12 SCID mice were measured by unidirectional immunodiffusion assay.Results21 out of 29 mice developed tumors in their body. Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell markers (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. The tumors can be diagnosed as human B-cell lymphomas by these morphological and immunohistochemical features. In situ hybridization exhibited resultant tumor cells had EBV encoded small RNA-1 (EBER-1). Human-derived IgG could be found in the serum from SCID mice on the 15thday following hu-PBL transplantation, and IgG levels increased with the tumor development in 6 hu-PBL/SCID chimeras.ConclusionsIntraperitoneal transfer of hu-PBLs from EBV+ donors to SCID mice leads to high human IgG levels in mouse serum and B cell lymphomas. Our findings suggest that increasing levels of human-derived IgG in peripheral blood from hu-PBL/SCID mice could be used to monitor EBV-related human B-cell lymphoma development in experimental animals.