Functional aspects of B cell autonomy in human thyroid disease

To evaluate the functional aspects of B cell autonomy in human autoimmune thyroiditis we examined antigen-dependent antibody secretion using specific PFC assays for total immunoglobulin and antibodies to human thyroglobulin (hTg) and SRBC. A microculture system based on S. aureus and a macrophage-derived B cell differentiating factor provided the essential data on specific antigen induction of B cells in macrophage-depleted cultures of peripheral mononuclear cells (PMC). Anti-SRBC PFC were readily induced by SRBC-antigen in normal PMC but a significant reduction in responses was observed in patients with autoimmune thyroiditis. 8 of 10 patients had anti-hTg PFC and none were observed in normal controls. However, only 3 patients showed hTg-antigen specific B cell induction. Varying mitogen and antigen concentrations, presentation of hTg in soluble or membrane bound forms, and adding helper and macrophage cell activity failed to induce specific hTg-antigen induction in the non-responsive patients. In conclusion, anti-hTg PFC were observed in the majority of patients with autoimmune thyroiditis but such B cell secretion was not usually subject to normal immunological control mechanisms. Furthermore, the reduced anti-SRBC response in patients indicated that non-specific abnormalities were also present in this organ specific disease.