Antigen- and receptor-driven regulatorymechanisms. The failure of idiotype- coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matehed targets

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Abstract
A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected i.v. into naive animals, stimulate suppressor T cell (Ts) responses. 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 i.v. to syngeneic BALB/c mice, failed to induce tolerance in these animals. 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. The failure of CRI-coupled spleen cells to induce Ts-mediated unresponsiveness in animals unable to express the appropriate VH [H chain variable region] 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 VH genes in the recipient animal is a prerequisite for Ts function was supported by the observation that Ts 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 Ts function. These Ts are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Thus, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of Ts function in ABA-specific suppressor pathways.