Human-specific Alu detection by PCR. Part 2

Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell marker (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. By these morphological and immunohistochemical features, those tumors can be diagnosed as human B-cell lymphomas. Furthermore, Alu-PCR showed that all of tumor tissues contained 221 bp Alu sequence. It confirmed that the induced tumors in hu-PBL/SCID mice were derived from human, but not from mouse.

In biopsy tissue, localization of EBER transcripts by in situ hybridization remains the gold standard for identifying latent infection of EBV. The in situ hybridization signal of EBER1 probe was very intense with a diffuse pattern of staining confined to the nucleus (sparing the nucleus) in all cases (Figure 3). Notably, almost all morphologically malignant cells exhibited a positive signal with the EBER1 probe, while the normal host tissue adjacent to tumor cells showed negative.

In the 12 mice whose IgG was examined, human serum IgG could be found in 6 SCID mice on day 15 after the engraftment of hu-PBLs and the IgG concentrations increased with the prolongation of the experiment, and then visible tumors developed. Marked elevations of human serum IgG levels in hu-PBL/SCID mice are associated with EBV-related lymphoma development. Human serum IgG levels from hu-PBL/SCID mice can be considered as a useful index of prediction for oncogenesis and tumor development. In contrast, IgG could not be detected both in the 3 mice with micro-lymphoproliferative lesions only and in the other 3 mice with no tumors during the experimental course. Additionally, our data showed human IgG concentrations in the serum of each of hu-PBL/SCID chimeras were also positively related to the serum IgG levels from different donors.


With the development of human organ transplantation and the increase of AIDS cases in recent years, both lymphoproliferative disease (LPD) in the immunocompromised patients and its relationship with EBV have become increasingly followed with interest. Clinically, almost all post-transplantation lymphomas are associated with EBV infection. Post-transplant lymphoprolifertive disorder (PT-LPD) is a syndrome of uncontrolled lymphoid growth in the immunosuppressed transplant patient. In the patients with PT-LPD, the incidence varies from 0.5% after bone marrow transplantation to 12% after heart-lung transplantation. PT-LPD remains so far a complication with a high morbidity and mortality. EBV is associated with posttransplant lymphoproliferative disease (PTLD), which is a leading cause of cancer death in recipients of transplants. On the other hand, investigations for AIDS-related lymphomas show that about 50-80% of those tumors are concerned with EBV. The vast majority of AIDS-NHL belongs to three kinds of high-grade B-cell lymphomas: Burkitt’s lymphoma, immunoblastic lymphoma, and large-cell lymphoma. Although there are some differences between this immunodeficiency-associated lymphoproliferative disorders, they share several common features: a tendency to present in extranodal sites, rapid clinical progression when untreated, diffuse large cell histology, B-cell origin and association with the EBV. The occurrence of lymphoma needs the activation, proliferation and transform of B-cell, as well as the development of malignant phenotype. The present experiment showed that B-cell lymphoma in the hu-PBL/SCID chimeras was similar to EBV-related neoplasms in the immunocompromised patients, so it could further indicate that immunodeficiency of animal or human body is an essential condition for the tumorigenesis.