Abnormal regulation of immunoglobulin synthesis in vitro in primary biliary cirrhosis

Abstract

To determine whether there is a defect in immune regulation in patients with primary biliary cirrhosis (PBC), T-cell mediated help and suppression of pokeweed mitogen-induced immunoglobulin (IgM and IgG) synthesis were studied in vitro. Cultures containing unirradiated T cells and B cells from normal individuals showed augmentation of immunoglobulin (Ig) synthesis at low T:B-cell ratios (helper T-cell effect) and inhibition of Ig synthesis at high T:B-cell ratios (suppressor T-cell effect). Cultures containing irradiated T cells from normal individuals showed augmentation of Ig synthesis at all T:B-cell ratios studied, indicating marked reduction of suppressor T-cell function by irradiation. In contrast, cultures containing unirradiated T cells and autologous B cells from patients with PBC showed augmentation of Ig synthesis at high T:B cell ratios. Immunoglobulin synthesis by cultures containing irradiated T cells and autologous B cells from patients with PBC was similar to that by corresponding cultures of cells from normal subjects. Allogeneic mixtures of cells from normal individuals and patients with PBC showed that while B cells from patients with PBC synthesize normal amounts of Ig in the presence of normal T cells, T cells from patients with PBC caused marked enhancement of Ig synthesis by normal B cells. Patients with other liver diseases characterized by chronic cholestasis, cirrhosis, or hepatocellular necrosis did not exhibit an analogous abnormality of Ig synthesis in vitro to that found in PBC. Primary biliary cirrhosis is associated with a defect of immune regulation characterized by abnormally high Ig synthesis by cultures of autologous T and B cells at high T:B cell ratios, which may be due to a deficiency of suppressor T-cell function.