EPSTEIN-BARR-VIRUS (EBV)-ASSOCIATED LYMPHOPROLIFERATIONS IN SEVERE COMBINED IMMUNODEFICIENT MICE TRANSPLANTED WITH HODGKINS-DISEASE LYMPH-NODES - IMPLICATION OF EBV-POSITIVE BYSTANDER B-LYMPHOCYTES RATHER THANEBV-INFECTED REED-STERNBERG CELLS

To establish an in vivo model for the study of Hodgkin's disease and R eed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hod gkin's disease were grafted into severe combined immunodeficiency (SCI D) 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 tu mors (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 l ymphoma and reactive lymph nodes). The relatively high number of EBV-p ositive small lymphocytes detected in Hodgkin's disease and T-cell lym phoma compared with B-cell lymphoma may account for the greater percen tage of EBV-positive tumors obtained in SCID mice. Our results show th at SCID mice do not provide the growth conditions that are required fo r in vivo growth of RS cells. We noted in some SCID tumors, the presen ce of binucleated and/or multinucleated giant cells resembling RS cell s. However, the presence of such cells was not restricted to mice graf ted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were lust binucleated E BV-positive lymphoblastoid cells rather than actual RS cells. (C) 1996 by The American Society of Hematology.