Trinitrobenzenesulphonic acid-induced unresponsiveness at the systemic level.
To investigate the mechanism underlying B-cell tolerance, which is still discussed as being the consequence of (functional) clonal deletion or suppression, limiting dilution (LD) analysis of the frequencies of B cells as well as regulatory cells after tolerance induction with trinitrobenzenesulphonic acid (TNBS) was performed. It was shown that the frequency of functionally active hapten-specific B cells was decreased to less than 10% of the frequency in untreated BALB/c mice. After an immunogenic challenge, trinitrophenyl (TNP)-specific B cells of tolerized mice expanded, but did not reach the level of TNP-specific B cells in untreated mice. The expansion of TNP-specific B cells in TNBS-tolerized mice after challenge with TNP-horse red blood cells (HRBC) as observed in LD cultures was in contrast to the absence of anti-TNP plaque-forming cells (PFC) in freshly harvested spleen cells (SC) and the non-detectability of anti-TNP antibodies (AB). Hence, the functional deletion (= anergy) of B cells in vivo appears to be sustained by regulatory cells. Analysis of the regulatory compartment revealed that tolerance induction resulted in transient augmentation of TNP-specific helper T cells (TH), continuously elevated levels of suppressor T cells (TS), and a low level of contrasuppressor T cells (TCS). But, contrary to non-tolerized mice, TCS of tolerized mice were rather refractory to stimulation with TNP-HRBC. Hence, we would like to hypothesize that clonal anergy of B cells leads to inappropriate activation of TCS, whose nominal antigens are antibodies. This in turn sustains the persistence of high levels of TS, i.e. tolerance would be maintained by interruption of feedback activation of regulatory cells via effector cells/molecules.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D006241:Haptens / Q000276:immunology*; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009578:Nitrobenzenes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology*
D006241:Haptens; D009578:Nitrobenzenes; D014302:Trinitrobenzenesulfonic Acid