The in vitro production of antibodies to mitochondrial antigens by peripheral blood mononuclear cells from patients with primary biliary cirrhosis.

Abstract

Peripheral blood mononuclear cells from 7 patients with primary biliary cirrhosis and 7 healthy control subjects were studied for their ability to produce antibodies to mitochondrial antigens in vitro. Peripheral blood mononuclear cells were collected by lymphapheresis and cultured with or without pokeweed mitogen for 10 days. The culture supernatants were then tested for antibodies to mitochondrial antigens by both immunofluorescence microscopy and a microtiter ELISA. Peripheral blood mononuclear cells from 5 of 7 patients with primary biliary cirrhosis but from none of the healthy controls produced antibodies to mitochondrial antigens spontaneously (without pokeweed mitogen stimulation). In contrast, peripheral blood mononuclear cells from 6 of 7 patients with primary biliary cirrhosis and from 6 of 7 control subjects synthesized detectable levels of antibodies to mitochondrial antigens after stimulation with pokeweed mitogen. In general, peripheral blood mononuclear cells from the primary biliary cirrhosis patients produced higher titers of antibodies to mitochondrial antigens in culture than cells from healthy controls. Furthermore, the antibodies to mitochondrial antigens reactivity produced by peripheral blood mononuclear cells of primary biliary cirrhosis patients exhibited a specificity for the M2 mitochondrial antigen which is present on the inner membrane of mitochondrial cristae and which is closely associated with a mitochondrial ATPase activity. In contrast, the antibodies to mitochondrial antigens reactivity produced by peripheral blood mononuclear cells of healthy controls appeared to be directed at a broader range of mitochondrial antigens. These findings indicate that, inpatients with primary biliary cirrhosis, there is a marked expansion of B lymphocyte clones that produce an antibody to a specific mitochondrial antigen.