Carrier-induced tolerance to nucleic acid antigens.

BALB/c and SJL mice were treated with nucleosides-IgG1 as a tolerogen, before either primary or secondary immunization with nucleosides-keyhole limpet hemocyanin. Nucleoside-specific responses were measured serologically by a modified Farr assay, with either 14C-labeled denatured DNA or nucleosides-131-I-labeled BSA as test antigen. Specificity of the response was tested by hapten inhition experiments. Multiple doses of nucleosides-IgG1 tolerogen given before the primary or secondary immunization effectively suppressed the secondary and tertiary anti-nucleoside responses. The tolerogen did not suppress the response to an unrelated hapten-KLH conjugate. The IgG alone did not suppress the anti-nucleoside response of BALB/c mice to nucleosides-KLH. Single doses of tolerogen before the primary or secondary immunization were less effective. Residual antibody in partially suppressed BALB/c mice showed changes in specificity as compared to controls. Suppression of the secondary response of SJL mice was measured much more readily by binding of nucleosides-131-I-BSA than by binding of denatured DNA. This reflected an altered specificity of the residual antibody; in control animals, antibodies were directed against all four nucleosides, whereas the antibodies of partially suppressed animals were directed only against guanosine. Suppression of anti-nucleic acid antibody responses may have therapeutic application in the management of systemic lupus erythematosus.