Regulation of Allotype-Linked NP^b Idiotype by an Idiotype-Positive Soluble Factor Derived from a T Cell Hybridoma

Abstract

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 (NP^b) positive T suppressor factor (NP^b-TsF) derived from a T cell hybridoma 7C3–13 of B10.BR (Igh-1^b, H-2^k) mouse origin. NP^b-TsF could suppress the responses mounted by primed spleen cells of all IgV_H compatible strains regardless of their H-2 haplotypes. The majority of the anti-NP antibody response suppressed by NP^b-TsF was idiotype positive (Id⁺). NP^b-TsF was also capable of suppressing the responses of H-2 compatible but Igh incompatible strains where responding cells do not produce NP^b idiotype. NP^b-TsF was incapable of suppressing the responses of mouse strains who are incompatible both in IgV_H and H-2 loci, indicating that the identity in either IgV_H or H-2 genes between NP^b-TsF and responding cells was necessary for the initiation of the suppression by NP^b-TsF. It was further found that the NP^b-TsF utilizes anti-idiotypic Lyt-1⁺2⁺3⁺ T cells (transducer cells), which are present only in IgV_H compatible strains, to ultimately suppress the Id⁺ antibody production by B cells. These results indicate that there exists a pathway where an idiotypic NP^b-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.