Depressed antibody responses to exogenous antigens in mice with lupus-like graft-versus-host disease

Previous work has established that a disease resembling systemic lupus erythematosus (SLE) can be induced in certain nonirradiated F1 mice undergoing a suitable graft-versus-host reaction (GVHR), e.g., (C57BL/10 X DBA/2)F1 mice injected with DBA/2 T cells. Here, we studied the antibody responses of such autoimmune graft-versus-host F1 mice to exogenous antigens, i.e., sheep erythrocytes, trinitrophenyl keyhole limpet hemocyanin, and levan. We found that primary antibody responses, in particular of IgG isotype, to the T-dependent antigens, sheep erythrocytes, and trinitrophenyl keyhole limpet hemocyanin were strongly suppressed during the entire observation period. Secondary anti-sheep erythrocyte responses, however, were normal, although the peak response was delayed for about 3 days. In contrast to the long-lasting depression of responses to T-dependent antigens, primary antibody responses to the T-independent antigen levan were depressed only at an early stage (i.e., week 2) of the graft-versus-host reaction. In spite of their depressed antibody responses to exogenous antigens, the graft-versus-host F1 mice showed increased numbers of spleen cells spontaneously secreting IgG, and produced IgG autoantibodies characteristic of systemic lupus erythematosus. Mixing experiments performed in vitro with cultures involving graft-versus-host spleen cells revealed that the decreased antibody formation cannot be attributed to suppressor T cells nor to a defect in helper T-cell function. Instead, the mechanism of decreased immune reactivity in SLE-like GVHR seems to operate at the level of B cells. Parallels between the decreased immune reactivity observed in lupus-like GVH disease and that described in human SLE as well as in spontaneously arising murine SLE are discussed.