Rejection of tumors of the B cell lineage by idiotype-vaccinated mice

Idiotypic determinants of immunoglobulins of malignant B lymphocytes and pl asma cells are tumor-specific antigens and have been used extensively in im munotherapy studies. The mechanisms involved in resistance to tumor challen ge following idiotype vaccination are poorly understood. Although a predomi nant role has been attributed to anti-idiotype antibodies, both humoral and cellular immune responses are probably involved. Cell-mediated responses m ay be particularly effective against tumor cell variants that do not expres s the idiotype on the cell surface and are therefore resistant to anti-idio type antibodies but continue to produce one of the original immunoglobulin polypeptides that may be processed and presented to T cells. In this report we describe two experimental models of idiotype vaccination in which antib odies are unlikely to play a role, and hence tumor immunity is attributed t o cell-mediated responses. One model consists of the murine B lymphocyte tu mor 38C-13 and its idiotype-negative variant DB2, which has lost the idioty pic specificity of the parental 38C-13 cell line through the production of a different light chain but expresses the original heavy chain. Vaccination of mice with the purified IgM of 38C-13 induced resistance to 38C-13 tumor cells as well as to the variant cells. Although immunized mice produced hi gh levels of anti-idiotype antibodies that bound to 38C-13 cells, no bindin g of antibodies to DB2 cells occurred. The finding that idiotype-vaccinated mice were resistant to idiotype-negative DB2 cells suggested that cellular mechanisms are involved in mediating resistance. The second model consists of the two plasma cell line JL mu s and JL mu m, which produce IgM with an identical specificity. Whereas one of them (JL mu s) secretes the IgM, the other one(JL mu m) can neither secrete nor deposit it on the cell surface. Immunization against JL mu s IgM followed by tumor challenge resulted in p rolonged survival of both JL mu s- and JL mu m-challenged mice. Although se ra of immunized mice contained high levels of anti-idiotype antibodies, the y did not react with the plasmacytoma cells. Similarly to the results obtai ned in the 38C-13 experimental model, these results suggest that a non-anti body-mediated mechanism was involved in the resistance of mice to tumor gro wth.