PREVENTIVE EFFECT OF IGG FROM EBV-SEROPOSITIVE DONORS ON THE DEVELOPMENT OF HUMAN LYMPHO-PROLIFERATIVE DISEASE IN SCID MICE

The effect of weekly treatments with various gammaglobulin preparation s an the development: of human B-cell tumors was studied in severe com bined immunodeficient (SCID) mice, SCID mice were injected i.p. with h uman peripheral blood mononuclear cells (PBMCs) from an Epstein-Barr v irus (EBV)-seropositive healthy blood donor, Repopulated SCID mice wer e divided into 7 treatment groups receiving either PBS, 2 commercial g ammaglobulin preparations, purified IgG prepared from pooled plasma fr om EBV-seronegative or -seropositive blood donors, a rabbit anti-serum against EBV envelope glycoprotein gp340 or interferon (IFN)-alpha, Al l treatments started I day after injection of PBMC and continued for 8 weeks, In the PBS-treated control group, 85% of mice developed tumors in the abdominal cavity, mostly with liver metastasis within 150 days , Tumor formation was prevented by treatment with the 2 commercial gam maglobulin preparations as well as by purified IgG from EBV-seropositi ve donors. In contrast, purified IgG from EBV-seronegative donors, rab bit anti-gp340 anti-serum or IFN-alpha had no effect, Our results indi cate that the effect of gammaglobulin is due to the presence of specif ic antibodies against EBV antigens, Further experiments showed that bo th the time of onset and the duration of treatment, as well as the dos e of Ig, are important factors for prevention of tumor formation. Stud ies aiming at identification of target antigens for antibodies which p revent lymphoma development may be clinically relevant for prevention and possibly treatment of lympho-proliferative disease in severely imm une-compromised patients. (C) 1997 Wiley-Liss, Inc.