Self-tolerance and autoimmunity in a minimal model of the idiotypic network

Abstract

We consider self-tolerance and its failure—autoimmunity—in a minimal mathematical model of the idiotypic network. A node in the network represents a clone of B-lymphocytes and its antibodies of the same idiotype which is encoded by a bitstring. The links between nodes represent possible interactions between clones of almost complementary idiotype. A clone survives only if the number of populated neighbored nodes is neither too small nor too large. The dynamics is driven by the influx of lymphocytes with randomly generated idiotype from the bone marrow. Previous work has revealed that the network evolves toward a highly organized modular architecture, characterized by groups of nodes which share statistical properties. The structural properties of the architecture can be described analytically, the statistical properties determined from simulations are confirmed by a modular mean-field theory. To model the presence of self we permanently occupy one or several nodes. These nodes influence their linked neighbors, the autoreactive clones, but are themselves not affected by idiotypic interactions. The architecture is very similar to the case without self, but organized such that the neighbors of self are only weakly occupied, thus providing self-tolerance. This supports the perspective that self-reactive clones, which regularly occur in healthy organisms, are controlled by anti-idiotypic clones. We discuss how perturbations, like an infection with foreign antigen, a change in the influx of new idiotypes, or the random removal of idiotypes, may lead to autoreactivity and devise protocols which cause a reconstitution of the self-tolerant state. The results could be helpful to understand network and probabilistic aspects of autoimmune disorders.