No abstract

The data presented in this manuscript extend our previous observations that recombinant interferon-gamma (reIFN-gamma) can suppress anti-immunoglobulin (anti-Ig)-stimulated B cell proliferation, and demonstrate that reIFN-gamma can also suppress B cell stimulation factor type 1 (BSF-1)-stimulated increases in expression of MHC class II molecules (Ia) on B cells. This suppression is most effective when relatively low concentrations of BSF-1 are employed, but is still very substantial even when optimal concentrations of BSF-1 were used. This suppression is also observed when size-separated small B cells which are devoid of detectable macrophages or NK cells are cultured with BSF-1 and reIFN-gamma, thus suggesting that IFN-gamma-mediated inhibition is a consequence of a direct effect on the B cells. Incubation of B cells with reIFN-gamma for 24 hr before their culture with BSF-1 did not prevent BSF-1-stimulated increases in sIa. This finding supports the contention that the effect of IFN-gamma is not mediated via the stimulation of "suppressor" influences in these cell cultures. The inhibition of B cell activation by IFN-gamma occurs within the first 3 hr after the onset of culture, as demonstrated by the inability of antibody to IFN-gamma to totally reverse the IFN-gamma-mediated suppressive effects on B cell proliferation if it is added later than 3 hr after the onset of culture. These results suggest a role for IFN-gamma in down-regulating the ability of B cells to function as antigen-presenting cells in non-cognate T cell-dependent responses.

Recombinant-derived interferon-gamma (reIFN-gamma) was found to inhibit B cell proliferation that was stimulated by soluble goat anti-mouse IgD or goat anti-mouse IgM antibodies, but not that stimulated by Sepharose-bound anti-Ig antibodies. Recombinant IFN-gamma also inhibited the BSF-1-enhanced soluble anti-Ig B cell proliferation but did not block BSF-1 enhancement of Sepharose anti-Ig-stimulated B cell DNA synthesis. Recombinant IFN-gamma concentrations as low as 0.001 U/ml were effective in suppressing the soluble anti-Ig-stimulated B cell proliferative response, and this inhibitory effect could be partially reversed by co-culture with a hybridoma anti-IFN-gamma antibody. Recombinant IFN-gamma appeared not to inhibit action of resting B cells from G0 to early G1, because it did not inhibit the increases in cell size that were stimulated by anti-delta antibody. However, it was effective in partially suppressing the anti-delta-induced increases in expression of B cell surface Ia. For reIFN-gamma to exert its maximum suppressive effect, it had to be added within the first 7 hr after the onset of culture with anti-Ig. Because reIFN-gamma is a lymphokine that can be detected in vivo, we suggest that it may play a key role in influencing physiologic B cell activation that is induced by antigens or immune complex-mediated cross-linking of surface Ig.

Tumor 85 adenocarcinoma cells, which are very weakly immunogenic for C3H/HeN (C3H) mice, provide a model tumor system for studying the parameters of induction of a cell-mediated immune response which does not appear to be a traditional cytotoxic T-cell or NK-cell response. Mice pre-immunized with irradiated tumor 85 cells are protected about 50% of the time from a challenge of viable tumor 85 cells although it is never possible to protect 100% of the immunized mice. Optimal protection is observed in mice immunized with 10(6) irradiated tumor 85 cells 14 days prior to challenge. Protection is also observed if mice are immunized with Protection is also observed if mice are immunized with 3H or C3HfeB/HeN (C3Hf) tumors originally induced by the same carcinogen as that used to induce tumor 85. The injection of carrageenan 1 h before challenge completely reverses the protection observed in immunized mice and and tumors grow faster in carrageenan-treated immunized mice than in normal mice. Two populations of cells obtained from cultures of spleen cells stimulated by tumor 85 cells appear to prevent tumor growth in vivo. One population, which is cytotoxic for tumor 85 cells in vitro, is nylon-wool-adherent and expresses Thy 1.2. The second population, which is not observed to be cytotoxic in a 51Cr release assay, is phagocytic.