Lymphocytes from patients with primary biliary cirrhosis spontaneously secrete high levels of IgG3 in culture.

The origin of the raised serum IgG3 in primary biliary cirrhosis has been examined. Blood lymphocytes from patients with PBC and from age- and sex-matched controls were cultured, and the culture supernatants were assayed for IgG and IgG3. Lymphocytes from PBC patients spontaneously synthesized a higher percentage IgG3/total IgG than did control lymphocytes, as determined by ELISA. The increased synthesis of IgG3 in culture correlated with serum IgG3 in the patients. This strongly suggests that the raised serum IgG3 in these patients is due to increased synthesis of this isotype. Following PWM stimulation, the proportion of IgG3/IgG synthesized by normal (and most PBC) lymphocytes increased and the difference in IgG3 synthesized by PBC and control lymphocytes became less marked. The kappa/lambda light chain ratio of the IgG3 was assayed by ELISA but no evidence was found for clonally restricted synthesis of IgG3 by PBC blood lymphocytes.