In vitro production of antimitochondrial antibody by peripheral blood mononuclear cells in patients with primary biliary cirrhosis.

Peripheral blood mononuclear cells from patients with primary biliary cirrhosis (PBC) were studied for their ability to produce antibodies to mitochondrial antigens (antimitochondrial antibody, AMA and anti-pyruvate dehydrogenase complex, anti-PDC), using dot-immunobinding and ELISA assay. 2 x 10(6) B cells alone and the mixture of 1.4 x 10(6) T plus 0.6 x 10(6) B cells from patients with serum AMA+ PBC spontaneously produced similar amounts of AMA and anti-PDC. Coculture experiments of T and B cells showed that anti-PDC production was significantly greater in pokeweed mitogen (PWM)-stimulated cultures than in unstimulated ones. The reactivities of antibodies to mitochondrial antigens were inhibited by M2 mitochondrial antigen-enriched fraction. Ursodeoxycholic acid added to cultures resulted in a significant inhibition for production of immunoglobulins and anti-PDC (IgG and IgM). Spontaneous production of AMA or anti-PDC was not detected in patients with AMA- PBC, chronic viral hepatitis and healthy controls, nor could it be induced by PWM in either group. EBV-transformed B cell line established from a AMA+ PBC patient produced high levels of AMA and IgM class anti-PDC. These findings indicate that antibody to a specific mitochondrial antigen in patients with PBC may be produced in T cell-dependent and-independent manner.