Gamma‐globulin modulates growth of EBV‐derived B‐cell tumors in scid mice reconstituted with human lymphocytes

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Abstract
The effect of weekly γ‐globulin injection on the development of human B‐cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein‐Barr virus (EBV)‐seropositive donors. Animals repopulated with cells from 5 donors received γ‐globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fatal EBV‐derived human B‐cell tumors was noticed in the γ‐globulin‐treated groups as compared to the controls. In a separate experiment, the effect of γ‐globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20‐week treatment. The results from this experiment showed that B‐cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first γ‐globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that γ‐globulin reduces the frequency of EBV‐derived B‐cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lymphoproliferative disorders associated with immunosuppression.