The induction of hapten-specific immunological tolerance and immunity in B lymphocytes. VI. Differential tolerance susceptibility in adult spleen as a function of B-cell maturation level.
The maturation level of the B-lymphocyte subpopulations involved in trinitrophenyl (TNP)-specific immunological tolerance in adult mice induced by the injection of trinitrobenzenesulfonic acid (TNBS) was investigated using in vitro antigen-specific and nonspecific polyclonal stimulation. The maturity of the B-cell subsets being studied was defined by the antigen or polyclonal activator which evoked a response. Thus, the thymic independent (TI-1) antigen TNP-lipopolysaccharide (TNP-LPS) and the polyclonal stimulant LPS were used to activate immature, neonatal-type B lymphocytes, whereas mature, adult-type B cells were responsive to the TI-2 antigen, TNP-Ficoll, and the nonspecific activator, purified protein derivative (PPD). Whereas unresponsiveness in TNP-LPS-reactive (immature) B cells 4 d after TNBS treatment was previously shown to be the result of functional deletion, partially reversible receptor blockade was detected in this study early after tolerogen treatment. By the 24-h point, tolerance was irreversible, as assessed by 24-h of antigen-free incubation and cocultivation of tolerant cells with control splenocytes. Tolerance was induced more rapidly in immature, TI-1 B cells than in mature TI-2 B lymphocytes. B lymphocytes reactive to TNP-Ficoll were also less susceptible to receptor blockade. Using LPS as a nonspecific probe for immature B cells, 60% tolerance in high affinity TNP-specific cells was induced within 12 h of TNBS treatment, and complete unresponsiveness by 24 h. In contrast, no significant decrease in response to the mature B-cell activator, PPD, occurred until day 2. Furthermore, the 50% tolerance level was achieved in TNP-specific LPS-reactive B cells by 100 times less tolerogen than required for PPD-responsive cells. Thus, TNBS-induced unresponsiveness in cells reactive to TNP-LPS is initially a result of reversible receptor blockade which leads within 4 d to functional deletion. Immature, TI-1 B lymphocytes, which give polyclonal responses to LPS and antigen-specific responses to TNP-LPS, are rendered tolerant to TNBS more rapidly and at lower tolerogen does than mature, TI-2 mouse B cells which react polyclonally to PPD and specifically to TNP-Ficoll. Moreover, these data show that both the immature and the mature B lymphocyts with these characteristic tolerance susceptibilities and specific and nonspecific immune response patterns are present in the adult mouse spleen.
D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005362:Ficoll / Q000276:immunology; D006241:Haptens / Q000008:administration & dosage*; D007108:Immune Tolerance; D008070:Lipopolysaccharides / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D006241:Haptens; D008070:Lipopolysaccharides; D014373:Tuberculin; D005362:Ficoll; D014302:Trinitrobenzenesulfonic Acid