EPSTEIN-BARR VIRUS-INDUCED HUMAN B-CELL LYMPHOMA ARISING IN HUPBL-SCID CHIMERIC MICE - CHARACTERIZATION AND THE ROLE OF CD40 STIMULATION INTHEIR TREATMENT AND PREVENTION

The transfer of human peripheral blood lymphocytes (huPBL) from EBV-se ropositive donors into mice with severe combined immune deficiency (SC ID) has been shown previously to result in the generation of human EBV -induced B-cell lymphomas, These lymphomas are similar to the aggressi ve lymphomas that arise clinically in immunocompromised individuals, W e have assessed the p53 status of these human B-lymphomas and the clon ality of cell lines established from tumors growing in the huPBL-SCID mice, While the lymphoma cell lines were demonstrated to be pauciclona l by Southern analysis, none of the lines demonstrated mutated p53 as determined by immunoprecipitation studies using antibodies specific fo r mutant p53, The cell lines were all positive for CD40, a marker pres ent on normal and neoplastic B cells, Antibodies to CD40 significantly inhibited the growth of these EBV-transformed B-cell lymphomas both i n vitro and in vivo, When partially purified human B cells were incuba ted with either anti-CD40 or anti-IgM in the presence of EBV-containin g supernatants in vitro, only anti-CD40 prevented transformation by EB V, Treatment of huPBL-SCID mice with anti-CD40 also prevented the occu rrence of the EBV lymphomas, However, long-term human B-cell engraftme nt was not inhibited as determined by the presence of serum human immu noglobulin in the chimeric mice, Overnight incubation of the huPBL wit h anti-CD40 did not prevent the incidence of lymphomas in huPBL-SCID c himeras suggesting that continuous exposure to anti-CD40 is required, These studies suggest that anti-CD40 may be of significant clinical us e in the treatment or prevention of EBV-induced B-cell lymphomas.