Epstein‐Barr virus status and tumour cell phenotype in sporadic Burkitt's lymphoma

Abstract

Burkitt's lymphoma (BL) biopsy cells and derived cell lines can be grouped according to their patterns of reactivity with 6 selected monoclonal antibodies (MAbs) against B cell‐associated surface antigens. Group I cells react only with MAbs J5 and 38.13, recognising the common acute lymphoblastic leukaemia antigen and a BL‐associated antigen respectively; group II cells react with J5 and 38.13 and with one or more of a set of MAbs (Ki‐24, MHM6, AC2, Ki‐I) against “lymphoblastoid” antigens; group III cells react only with these anti‐“lymphoblastoid” MAbs. Tumour biopsy cells from 17 cases of sporadic BL, 9 positive for the Epstein‐Barr (EB) virus genome and 8 negative, have been analysed during the process of cell line establishment in vitro. In early passage the EB virus‐negative BL cells showed either a group I phenotype or gave an additional reactivity with MAb Ki‐24 which placed them in group II; these phenotypes remained essentially stable with continued growth of the cell lines for up to 50 passages. By contrast the EB virus‐positive BL cells were much more susceptible to phenotypic change in vitro. Although such cells displayed a group I or group II phenotype in early passage, many of the lines soon moved into group III whilst retaining the karyotypic markers indicative of their malignant origin. These observations suggest that a resident EB virus genome can drive the in vitro progression of BL cells towards a more “lymphoblastoid” phenotype. This was confirmed in subsequent experiments where virus‐negative BL cell lines were converted to EB virus positivity by in vitro infection. Clearly, therefore, phenotypic analysis of long‐established lines can lead to false distinctions being drawn between the EB virus‐positive and ‐negative forms of sporadic BL; both may derive from the same sub‐population of target B cells in vivo.