Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Blood. 1996 Mar 15;87(6):2435-42. Unique Identifier : AIDSLINE MED/96203812
Meggetto F; Muller C; Henry S; Selves J; Mariame B; Brousset P; Saati TA; Delsol G; Department of Hematology, CHU-Purpan, Toulouse, France.

Abstract: To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV-positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV-positive lymphoma blastoid cells rather than actual RS cells.

Keywords: Adult Aged Animal B-Lymphocyte Subsets/*PATHOLOGY/TRANSPLANTATION/VIROLOGY Cell Lineage *Cell Transformation, Viral Child Child, Preschool Clone Cells/PATHOLOGY/VIROLOGY Comparative Study Female Graft Survival Herpesviridae Infections/PATHOLOGY/*TRANSMISSION/VIROLOGY Herpesvirus 4, Human/ISOLATION & PURIF/*PATHOGENICITY Hodgkin's Disease/PATHOLOGY/*VIROLOGY Human Immunophenotyping Lymph Nodes/PATHOLOGY/*TRANSPLANTATION/VIROLOGY Lymphoproliferative Disorders/ETIOLOGY/PATHOLOGY/*VIROLOGY Male Mice Mice, SCID Middle Age Neoplasm Transplantation Reed-Sternberg Cells/*PATHOLOGY/TRANSPLANTATION/VIROLOGY Severe Combined Immunodeficiency/COMPLICATIONS Support, Non-U.S. Gov't Transplantation, Heterologous Tumor Virus Infections/PATHOLOGY/*TRANSMISSION/VIROLOGY JOURNAL ARTICLE
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