Simulation analysis of the mechanism of escape from immunoglobulin suppression.

The mathematical model of B cell tolerance was applied to idiotype and isotype suppression of short duration induced in mice by neonatal application of monoclonal antibodies specific for the respective immunoglobulin determinants. Suppressor cells play an important role in chronic idiotype or isotype suppression, but these suppressions of short duration seem to be caused by direct elimination of B cells by the injected antibodies. The recovery from suppression of short duration starts, when the injected antibody is eliminated from the organism and is caused by differentiation from stem cells of new B lymphocytes possessing the respective immunoglobulin markers. This mechanism is analogous to that assumed for immunological tolerance in the mathematical model except that the injected monoclonal antibody plays the role of tolerance-inducing antigen. However, satisfactory agreement of simulated values with the experimental ones could not be obtained, if experimentally observed elimination rate of the injected antibody was used for calculations. A better fit was obtained with elimination rate values decreasing with age which do not correspond to the actual ones of the injected antibody. At present, we do not know which mechanism is described by these "virtual" elimination rates.