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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.
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