Low expression of CD20 and CD23 in Epstein-Barr virus-induced B cell tumors in SCID/hu mice

Abstract

Intraperitoneal injection of immunodeficient C.B.-17/scid (SCID) mice with human peripheral blood leukocytes from Epstein-Barr virus (EBV)-seropositive donors or with peripheral blood leukocytes from EBV-seronegative donors followed by an injection of EBV results in the development of human B-cell tumors. EBV-induced oligoclonal SCID/hu tumors closely resemble the EBV-associated lymphoproliferative disorders that are complications in immunosuppressed transplant patients. Previous reports have indicated that SCID/hu tumor cells are phenotypically similar to in vitro-transformed lymphoblastoid cell lines (LCL), which express high levels of mature B-cell lineage/activation antigens (CD19, CD20, CD21, CD23, CD30, CD39). In this study, however, flow cytometric (FACS) analysis showed that expression of CD20 and CD23 by SCID/hu tumor cells was markedly reduced relative to CD20 and CD23 expression by donor-matched, in vitro-transformed LCL. Injection of LCL into SCID mice also produced tumors in which CD20 and CD23 expression was greatly reduced relative to levels expressed by the injected LCL. In addition, tumorigenesis following LCL injection was associated with the production of high levels of human Ig in the sera of SCID mice. Our data thus indicate that EBV-driven tumorigenesis in vivo is associated with significant changes in B-cell phenotype relative to EBV-infected B cells transformed in vitro.