Regulation of allotype-linked NPb idiotype by an idiotype-positive soluble factor derived from a T cell hybridoma. Coupling of the circuit regulation to the network concept.
We reported in this paper genetic requirements for the suppression of anti-4-hydroxy-3-nitrophenylacetyl (NP) antibody response induced by an NP-specific, Igh-1 linked idiotype (NPb) positive T suppressor factor (NPb-TsF) derived from a T cell hybridoma 7C3-13 of B10.BR (Igh-1b, H-2k) mouse origin. NPb-TsF could suppress the responses mounted by primed spleen cells of all IgVH compatible strains regardless of their H-2 haplotypes. The majority of the anti-NP antibody response suppressed by NPb-TsF was idiotype positive (Id+). NPb-TsF was also capable of suppressing the responses of H-2 compatible but Igh incompatible strains where responding cells do not produce NPb idiotype. NPb-TsF was incapable of suppressing the responses of mouse strains who are incompatible both in IgVH and H-2 loci, indicating that the identity in either IgVH or H-2 genes between NPb-TsF and responding cells was necessary for the initiation of the suppression by NPb-TsF. It was further found that the NPb-TsF utilizes anti-idiotypic Lyt-1+2+3+ T cells (transducer cells), which are present only in IgVH compatible strains, to ultimately suppress the Id+ antibody production by B cells. These results indicate that there exists a pathway where an idiotypic NPb-TsF activates a suppressor circuit mediated via the idiotype-antiidiotype interactions apart from the previously described carrier-specific and H-2 restricted suppressor circuit. Both pathways involve the 'transduction' step utilizing Lyt-1+2+3+ intermediary T cells. Our experiments provide important clues for coupling the two major immunological concepts, network and circuit.
D000818:Animals; D000918:Antibody Specificity; D006241:Haptens / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D006825:Hybridomas / Q000276:immunology*; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000276:immunology; D012995:Solubility; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D006241:Haptens; D006649:Histocompatibility Antigens; D007126:Immunoglobulin Allotypes; D007130:Immunoglobulin Idiotypes; D009596:Nitrophenols; C026654:4-hydroxy-3-nitrophenylacetyl-O-succinimide ester; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin