Tolerance induction by continuous stimulation with dextran B512.

The thymus-independent antigen Dextran B512 was used to induce tolerance with immunogenic doses. We show the difficulty to obtain a steady state by administering weekly antigen doses. Three weekly doses were required to achieve tolerance or "homeostatic equilibrium". Three groups of mice (C57BL6 X CBA) F1 were stimulated with: a) 0.5 microgram Dextran one weekly dose for ten weeks. b) 2 micrograms Dex. one weekly dose, for twenty-two weeks, and c) 10 micrograms Dex. three times a week, administered continuously for eleven weeks. The number of anti-Dex. antibody secreting cells was determined by Cunningham and Szenberg PFC technique. Weekly continuous doses of 0.5 and 2 micrograms of antigen showed frequent fluctuations in IgM and unresponsiveness was not achieved. Nonetheless, a three times weekly dose of 10 micrograms Dex. showed IgM response with oscillations and little anti-Dex. IgG response was obtained. After eleven weeks of continuous stimulation the steady state was succeeded. This antigen triggered high levels of IgM bearing B cells in mice, and more difficult tolerance induction was known in this isotype, but also the stimulation model was an important fact in achievement of steady state.