Clonal dominance and the preservation of clonal memory cells mediated by antigen-antibody.
Selected B-cell clones and their well characterized monoclonal antibody products were used to analyse the role of antibody in clonal dominance and the regulation of memory cell supplies. The experimental design was to permit contact between spleen cells and antigen in vitro, and to administer antibody to DNP prior to or following cell transfers into irradiated recipients. The anti-hapten response was strongly suppressed by the clone's own antibody or higher affinity antibody administered on day 0. Antigen-antibody inhibited memory cell generation. The suppressive effect was temporary, and reversible with time and further antigen and the same clone could be induced to produce antibody again, analysed by isoelectric focusing. We were therefore not dealing with clonal deletion. Change in the source of clonal anti-hapten excluded possible effects of antibody to carrier protein or idiotypic determinants in this system. The timing of antibody administration indicates that clones already triggered in the first 4 days after antigen contact could not be suppressed by antibody. Passive antibody to DNP only suppressed when both B and T cells had been permitted contact with hapten-carrier protein. Alteration of the carrier protein enabled us to study the effect of antigen-antibody on B and T cells separately. B cells binding antigen and antibody to hapten were triggered more efficiently by fresh T cells recognizing the carrier protein than after antigen uptake alone. Antibody to DNP suppressed only when both B and T cells had taken up hapten-protein, suggesting that antigen-antibody acts centrally at the level of both B memory cells and T helper cells. This reversible antigen-antibody blockade appears to favour the preservation of a pool of long-lived memory cells rather than the priming of new clones developing from short lived precursor cells; clonal dominance ensues.
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins; D002999:Clone Cells / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology; D006241:Haptens; D007112:Immunity, Maternally-Acquired; D007156:Immunologic Memory; D007165:Immunosuppression Therapy; D007525:Isoelectric Focusing; D051379:Mice; D008808:Mice, Inbred CBA; D008954:Models, Biological; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D002352:Carrier Proteins; D004140:Dinitrophenols; D006241:Haptens