Antigen- and receptor-driven regulatory mechanisms. V. The failure of idiotype-coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matched targets.
A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected intravenously into naive animals, stimulate suppressor T cell (Ts) responses. Moreover, previous studies have demonstrated that the ability of such idiotype-coupled spleen cells to induce immune unresponsiveness to subsequent immunization with ABA-coupled spleen cells is linked to Igh-1 genes. Thus, CRI bearing antibodies from A/J mice, when conjugated to normal BALB/c spleen cells in vitro and then injected intravenously to syngeneic BALB/c mice, failed to induce tolerance in these animals. However, spleen cells taken from these animals transferred significant degrees of suppression to Igh-1 congenic C.AL-20 but not to H-2 congenic, Igh-1 distinct B10.D2 mice. Therefore, the failure of CRI-coupled spleen cells to induce suppressor cell- mediated unresponsiveness in animals unable to express the appropriate VH genes (i.e. BALB/c and B10.D2) appears to be caused by the lack of idiotype- matched targets. The notion that the ability to express certain Vn genes in the recipient animal is a prerequisite for suppressor cell function was further supported by the observation that suppressor cells induced in C.AL-20 mice failed to transfer any degree of suppression to BALB/c mice. The ability to transfer suppression from BALB/c mice to C.AL-20 mice is a T cell- dependent phenomenon, since in vitro treatment with anti-Thy 1.2 antiserum and complement completely abrogated suppressor cell function. Furthermore, these suppressor T cells are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Therefore, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of suppressor T cell function in ABA-specific suppressor pathways.
D000818:Animals; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000939:Epitopes; D007130:Immunoglobulin Idiotypes