The effect of second signals on the induction of B cell tolerance: failure of helper T cells to block tolerance induction.
The effect of carrier-primed helper T (Th) cells and T cell-replacing factors on the induction of hapten-specific tolerance in B cells from adult mice has been tested. The 2,4,6-trinitrophenyl conjugate of human gamma-globulin (TNP17HGG) was used as tolerogen in an in vitro tolerance induction system. Tolerance was assessed by the subsequent induction of plaque-forming cell responses using TNP-Brucella abortus and trinitrophenylated sheep red blood cells (TNP-SRBC) plus SRBC-primed Th cells as T-independent (TI) and T-dependent (TD) forms of TNP, respectively. B cells that respond to the different forms of TNP appear to be distinct B cell subpopulations. TNP17HGG induced TNP-specific tolerance in B cells responsive to TI and TD forms of the antigen, although more tolerogen was required to induce unresponsiveness in the TD antigen-reactive B cells. The presence of antigen nonspecific T cell-replacing factors during tolerance induction had no effect on the induction of unresponsiveness in either TI or TD antigen-responsive B cells, although these factors were able to support primary anti-TNP responses in T-depleted B cell populations to subtolerogenic doses of TNP-HGG. Populations of irradiated lymphocytes enriched for HGG-specific Th cells also had no effect on tolerogenesis in TI or TD antigen-responsive B cells, although priming of TD antigen-responsive B cells occurred at subtolerogenic doses of tolerogen. The inability of these Th cells to modulate B cell unresponsiveness was not due to their inability to exert helper function at higher concentrations of HGG. Thus, in this system, tolerance susceptibility is an intrinsic property of B lymphocytes, i.e. immunogenicity vs. tolerogenicity of signals is not determined by a "second signal" provided by Th cells.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003208:Concanavalin A / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006462:Hemolytic Plaque Technique; D007108:Immune Tolerance; D007114:Immunization; D007375:Interleukin-1; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology*; D005719:gamma-Globulins / Q000276:immunology
D007375:Interleukin-1; D011506:Proteins; D005719:gamma-Globulins; D003208:Concanavalin A