BALB/C MICE IMMUNIZED WITH EITHER XENOGENEIC OR SYNGENEIC TSH PRODUCE IMMUNOGLOBULINS WITH ANTI-TSH AND THYROID-STIMULATING ACTIVITIES

Balb/C mice were immunized with bTSH (xenogeneic TSH) or extracts of Balb/C pituitaries (containing syngeneic TSH), either intracutaneously with Freund's adjuvant or intrasplenically. After bTSH, all blood samples contained anti-TSH antibodies. Thyroid-stimulating activity was assayed on FRTL-5 cells. Of 80 sera from immunized mice, 33 induced an increase in (TcO4)-Tc-99m uptake, and 31/79 induced an increase in thyroidal [H-3]thymidine uptake by thyrocytes. With syngeneic TSH, anti-TSH antibodies were found in 10/19 mice. Immunoglobulins increasing thyrocyte technetium uptake were found in 14/19 mice, and immunoglobulins that stimulated thymidine uptake in thyrocyte DNA were detected in 12/19 sera. After immunization with both types of TSH, sera of some mice showed only one of the two bioactivities. Hybridomas were prepared with splenic lymphocytes of the mice immunized with either of the TSH preparations. These secreted TSH-binding immunoglobulins or immunoglobulins which stimulated thymidine or technetium uptake by the thyrocytes. One of the hybridomas from mice immunized with pituitary extract secreted a monoclonal antibody which stimulated thyroidal thymidine uptake, but inhibited bTSH-induced (TcO4)-Tc-99m uptake. These findings might suggest that the anti-idiotypic network acting on TSH as an antigen could be involved in the pathogenesis of stimulatory antibodies in thyroid disease.