Genetic differences in immune reactivity to mercuric chloride (HgCl2): Immunosuppression of H-2(d) mice is mediated by interferon-gamma (IFN-γ)

Upon treatment with HgCI2, H-2(s) mice, such as B10.S, develop an activation of B lymphocytes that depends, at least partially, on activation of T helper type 2 (Th2) cells and results in increased serum levels of IgG1 and IgE, appearance of IgG autoantibodies, and development of immune glomerulonephritis and vasculitis. Results of previous studies and of experiments presented here indicate that the B cell activation and systemic autoimmune disease fail to develop in MHC-congenic B10.D2 (H-2(d)) and B10.BR (H-2(k)) mice treated with HgCI2, although B10.D2 T cells showed signs of activation by and specificity for HgCI2 comparable to those seen in strain B10.S. Here, we report that following HgCI2 injections the antibody response to sheep erythrocytes is normal in B10.S, but suppressed in B10.D2 mice. This suppression was prevented by MoAb to mouse IFN-γ. Conversely, treatment of B10.D2 mice with murine recombinant IFN-γ, (rIFN-γ,) was able to reproduce the immunosuppression seen after HgCl2 treatment. In B10.S mice, it took administration of both rIFN-γ and HgCl2 to suppress the anti-sheep erythrocyte response. Although rIFN-γ diminished the increase in IgE serum levels of HgCI2-treated B10.S mice, it failed to prevent their autoantibody production and immune glomerulonephritis. These findings further strengthen the concept that B10.S mice react 10 HgCI2 by preferential activation of their Th2 cells producing IL-4, whereas B10.D2 mice react to HgCI2 by preferential activation of their Th1 cells, which produce IFN-γ and thus suppress antibody responses