Antitumor Activity Induced By Mouse Soluble B Lymphoctye Stimulator

B lymphocyte stimulator ( BlyS ) , a novel member of the TNF ligand superfamily, is a fundamental survival factor for B cells and plays an important role in humoral immune responses. In the present study, we constructed plasmid vectors encoding the murine soluble B lymphocyte stimulator (msBlyS) cDNA linked with the Igκ leader sequence to estimate the efficacy of the msBlyS vector and to evaluate msBlyS-producing tumor cells as a tumor vaccine. Colon 26 cells and LL/2 cells were transfected respectively with the above mentioned vectors or with vector alone(mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of msBlyS cDNA in msBlyS transfectants in comparison to that in mock transfected cells .The culture supernatants of msBlyS transfectants can costimulate murine spleenic B cells proliferation in vitro with anti-IgM antibody. When injected into syngeneic mice, the growth of msBlyS transfectants was significantly less than that in mock trasfected cells(P<0.01,by ANOVA and analysis of covariance). In addition, injection of colon 26 or LL/2 cells into mice immunized with a msBlyS transfectantrevealed acquired immunity. Autoantibodies against tumor cells were identified by Western bolt analysis and ELISA assay and anti-tumor autoantibody depositions could be detected in the msBlyS transfectants immunized mice. The anti-tumor activity could also be caused by the adoptive transfer of the immunoglobulins purified from msBlyS transfectants immunized mice serum . Depletion of CD8+T cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+T antibodies. These data suggest that the rejection of msBlyS/tumor cells was mediated through B-cell activation. Gene therapy using msBlyS transfectants containing a plasmid vector and the Ig k leader sequence may be a useful tumor vaccine.