Publication 2078

This article investigates the following basic question: in the relatively stable molecular environment of a vertebrate body, can a dynamic idiotypic immune network develop a natural tolerance to endogenous components? Our approach is based on stability analysis and computer simulation using a model that takes into account the dynamics of two agents of the immune system, namely, B-lymphocytes and antibodies. We investigate the behavior of simple immune networks in interaction with an Ag whose concentration is being held constant as a function of the connectivity matrix of the network. The latter is characterized by the total number of clones, N, and the number of clones, C, with which each clone interacts. The idiotypic network models typically become unstable in the presence of this type of Ag. We show that idiotypic networks that can be found in particular connected regions of NC-space show tolerance towards auto-Ag without the need for ad hoc mechanisms that prevent an immune response. These tolerant network structures provide dynamical regimes in which the clone which interacts with the auto-Ag is suppressed instead of being excited such that an unbounded immune response does not occur. Possible implications for the future treatment of auto-immune disease such as IvIg-treatment are discussed in the light of these results. Moreover, we propose an experimental approach to verify the results of the present theoretical study.