Dysfunction of immune system and induction of autoantibodies to liver antigens by neonatal thymectomy in mice.

We examined the development of autoantibodies to liver proteins and hepatitis in BALB/c mice thymectomized 2 days after birth and attempted to characterized the immune function of these mice. Autoantibodies to crude liver proteins detected by ELISA were found in 21 (84%) of 25 mice thymectomized 2 days after birth. In these mice, sera of 11 animals showed reactivity with both liver specific proteins (LSP) and the second fraction of crude liver proteins; sera of 3 mice showed reactivity with only the second fraction but sera showed reactivity with only LSP. By Western-immunoblotting, sera of BALB/c mice which showed high autoantibody level to liver proteins detected a strong band around 150kD in the second fraction of crude liver proteins. Still more, hepatic inflammation; mononuclear cell infiltration in the portal area, was induced in mice with apparently high autoantibody level to crude liver proteins. These results in BALB/c mice corresponded with our previous reports which employed C3H/HeN mice. Next, we examined immune functions of mice thymectomized 2 days after birth. In thymectomized mice, the proportion of Thy-1, L3T4 and Lyt-2 positive cells (T cells) decreased and the proportion of B220 positive cells (B cells) increased. The proliferative response of lymph nodes lymphocytes cultured with mitomycin C-treated syngeneic spleen cells was lower, and the total IgG level in the sera was higher when compared with control normal mice. Anti-nuclear antibody (ANA) also appeared in the sera of thymectomized mice 2 days after birth. All these results suggest that the dysfunction of T cell and polyclonal activation of B cell were induced in neonatally thymectomized mice and resulted in the production of ANA and autoantibodies to liver proteins.