Abnormal immune mechanisms are being studied in patients with primary biliary cirrhosis (PBC). T cell mediated help and suppression of pokeweed mitogen-induced immunoglobulin synthesis by B cells has been studied using radioimmunoassays to measure IgG and IgM synthesized by cultures containing appropriate mixtures of different lymphocyte subpopulations in vitro. The ability of T cells to proliferate when cultured with either autologous or allogeneic irradiated B cells (mixed lymphocyte reactions) or with hapten-modified autologous irradiated B cells has been assessed. Results of these studies include the demonstration in PBC of (i) a diminished capacity of T cells to inhibit immunoglobulin synthesis in vitro, (ii) a deficiency of the autologous but not the allogeneic mixed lymphocyte reaction and (iii) a deficiency in the primary but not the secondary proliferative response of T cells to hapten-modified cells. These findings suggest that in PBC there is a fundamental defect in the interaction between autoreactive T cells and surface antigens on autologous non-T cells which leads to diminished activation of suppressor T cells and, hence, predisposes to a state of immune hyperresponsiveness. The coexistence of IgA deficiency and PBC has been documented. Thus, while it is possible that IgA deficiency may contribute to the development of PBC, the pathogenesis of PBC does not require IgA-dependent mechanisms. Sera from patients with PBC has been shown to contain a factor, probably an abnormally immunoreactive IgM, which blocks the binding of C3b-opsonized erythrocytes by monocytes; this finding affords a potential explanation for the C3b-receptor specific clearance defect by fixed macrophages in PBC. Patients with PBC have been shown to have diminished natural killer cell activity due to a functional defect of cytolytic effector cells. Defects of humoral immunity in PBC appear to be due to activation of small subpopulations of B cells. For example, in PBC there is evidence compatible with an expanded clone of B cells that synthesize mitochondrial antibodies with different antigenic specificities from those synthesized by normal B cells. A disease-specific immunologic defect has yet to be defined in PBC.
