Search for tumor-specific immune reactions in Burkitt lymphoma patients by the membrane immunofluorescence reaction.

Virus-induced lymphomas of the mouse contain tumor-specific antigens, as evidenced by the rejection of small numbers of viable neoplastic cells by preimmunized, genetically compatible animals; and the concomitant appearance of antibodies, demonstrated by the cytotoxic reaction in vitro, or by the membrane immunofluorescence reaction with living target cells.'-10 In the course of previous studies, we have been particularly interested in lymnphomas induced by the Moloney virus.5' 10 When adult mice are inoculated with this agent, they develop high titers of antibodies, capable of reacting with Moloney lymphoma target cells in immunofluorescence and cytotoxic tests, but not crossreacting with lymphomas induced by the Gross or Graffi viruses.5' 11, 12 Mice inoculated with the Moloney agent when newborn often develop tolerance.13 Virus-neutralizing, cytotoxic, or fluorescent antibodies fail to appear and cannot be induced by a second virus inoculation at adult age.14 Mlice inoculated as newborn develop leukemia earlier and in a higher incidence than mice that received the agent for the first time at adult age. Animals of the latter category show a decrease of their usually high antibody titer when they develop generalized leukenlia. If leukemia is inhibited by chemotherapy, the antibody levels may rise again.15 Whether similar reactions occur in human malignancies of the lymphatic system is of interest. The Burkitt lymphoma has attracted much interest during recent years due to serious consideration of a possible virus etiology. All virus-induced murine neoplasms studied have been found to contain tumor-specific antigens capable of inducing host rejection reactions, with common specificity shared by all neoplasms induced by the same virus. The possible antigenicity of the Burkitt tumor is also indicated by the total regression of the disease after chemotherapy in a considerable proportion of cases and the absence of recurrence during observation periods up to 4-6 years. Such durable remissions have been obtained by different agents and even in cases where treatment was incomplete. According to Burkitt,'6 these good results cannot be attributed to an unusual susceptibility of the tumor to cytotoxic agents since this cannot explain spontaneous or temporary remissions following serum transfusions alone.24 It has therefore been postulated that some immunological mechanism operates. The purpose of the present study was to look for possible tumor-specific reactions in Burkitt lymphoma and, if found, to assess their significance. The choice of materials and methods was based on our experience in the Moloney system. Since different Moloney lymphomas showed great variation with regard to surface antigen concentration, and since variants with a decreased antigen concentration could be selected during passage in vitro or in vivo, we have worked with fresh biopsy material rather than with established cell lines. The membrane immunofluorescence