Generation of idiotype-specific T cell help through network perturbation.

Different manipulations of BALB/c mice were used to generate idiotype-specific help: neonatally induced suppression of the T 15 idiotype and low-dose priming with anti-T15 antibody. The splenic foci culture system was used to study T15-idiotype-recognizing helper T cells under limiting-cell-dose conditions. These treatments induced T15 idiotype-specific help for B cells responding to TNP-T15. Normal or hemocyanin-primed BALB/c mice did not supply T15 idiotype-specific help. The helper cells were sensitive to anti-Thy-1.2 and complement treatment and can distinguish T15 from an idiotype-different, PC-binding myeloma protein, M167, and the TNP binding myeloma protein, M460. These data show that idiotype-specific T helper cells can be induced by at least two different manipulations of the idiotype network. These manipulations presumably do not act directly on the T15-recognizing T cells, but must involve complementary idiotypic circuits that stimulate anti-T15 specific T cells. Furthermore, this study demonstrates that the splenic-fragment culture technique provides a general method to investigate, at the single cell level, idiotypic T-B cell interactions induced by perturbations of the immune network.