Days Post InocuIation ChaIIenge

n=10

vaccinated

n=10

vaccinated

Figure 5.12. LLC tumor progression and survival of C57BL/6 ||MT mice. Two groups of 10 mice were inoculated subcutaneously with LLC cells. Each of 10 LLC inoculated naïve mice are shown having varying sized tumors. The second group of mice had been vaccinated with irradiated LLC cells two weeks prior to challenge. None of these mice developed tumors as indicated by the arrow pointing to baseline. Tumor progression in each group was monitored several times weekly.

with LLC cells in order to identify the cellular and biochemical mediators that regulate B cell-mediated suppression of anti-tumor immunity, and to determine whether suppression can be reversed. Wild type C57BL/6 mice rapidly developed LLC tumors regardless of whether they had been vaccinated with irradiated LLC cells or not. C57BL/6 ^MT B cell deficient mice also developed tumors but at a slower rate whereas vaccination with irradiated LLC cells uniformly protected the mice from subsequent challenge. However, when the mice were reconstituted with C57BL/6 splenic B cells prior to vaccination the mice were no longer protected when challenged several weeks later with LLC tumor cells. Furthermore, when the mice were first vaccinated and later reconstituted with B cells and subsequently challenged with LLC all of the mice were protected. Thus, in order for B cells to suppress the development of anti-tumor immunity they had to be present in the mice prior to, or during, LLC vaccination (Figure 5.12). Using this H-2b restricted LLC tumor model we confirmed earlier observations made by Qin et al. in BALB/c (H-2d) B cell deficient mice. By showing that B cell-induced suppression of anti-tumor immunity occurs in an antigen-nonspecific manner, and is neither antibody-mediated or serum dependent (manuscript in preparation) we extended the findings of Qin and colleagues. Furthermore, suppression of anti-tumor immunity is not the sole province of B cells but can also be mediated by dendritic cells (Figdor et al., 2004; Munn et al., 2004) and regulatory T cells (Wei et al., 2004). We find that both dendritic cells, or CD4 T cells lacking CD25 expression, in addition to B cells from syngeneic wild type mice, can suppress the development of anti-tumor immunity to LLC in ^MT B cell deficient, or Rag-deficient mice

150 "I

3 mice

3 mice

Was this article helpful?

0 0

Post a comment