Augmentation of auto-anti-idiotypic antibody production by hapten-reactive helper T lymphocytes

Augmented auto-anti-idiotypic antibody production was effectively achieved by immunization of mice with haptenated myeloma protein in the presence of hapten-reactive helper T lymphocytes. Hapten-reactive helper T-lymphocyte activities were raised in BALB/c mice by immunization with para-azobenzoate (PAB)-derived mouse gamma globulin (MGG) prepared by amidination reaction (PAB_im-MGG). Helper T cell activity was effectively enhanced by pretreatment of mice with a PAB-derived nonimmunogenic copolymer of D-glutamic acid and D-lysine (D-GL) (PAB-D-GL) 3 days before priming with PAB_im-MGG; PAB-D-GL is a potent tolerogen of both PAB-specific suppressor T lymphocytes and PAB-specific B cells. After induction of these enhanced PAB-reactive helper T lymphocytes, mice were immunized with PAB-coupled TEPC-15 myeloma protein (PAB_im-T-15), which was also prepared by amidination reaction. Mice immunized in this way manifested strikingly enhanced titers of auto-anti-idiotypic antibodies, specific for the T-15 idiotype, as compared to control mice which had not been preimmunized with PAB_im-MGG. The ability of PAB_im-MGG preimmunization to facilitate auto-anti-idiotypic antibody production was due to the activity of PAB-reactive helper T cells since PAB-specific B cells had been abolished by prior treatment with PAB-D-GL. The implications of this model for future studies on immunological engineering the analysis of idiotype network phenomena are discussed.