A model of the immune network with B-T cell co-operation. II--The simulation of ontogenesis.

This paper is based on a new model of the immune network which explicitly incorporates B-T cell co-operation. A major feature of this model is the simplifying assumption that inhibition by anti-TCR soluble Ig is the only possible down-regulatory influence on activated T-cells. This model is capable of coupling with antigens in both an "immune response" mode and a "tolerant" mode. In the present paper, we simulate the ontogenesis of the immune system by metadynamical recruitment of T- and B-cell clones from the thymus and the bone marrow, seeking to identify the conditions under which each of these modes of antigen coupling occurs. Achieving the tolerant mode depends principally on four parameters: a high value of SB, the rate of bone-marrow production of B-cells; a relatively high efficiency of T-help through mIg-TCR recognition compared with (MHC + peptide)-TCR interaction; and a relatively high value of the product PR.NA, where PR is the average probability that an Ig recognizes another molecule and NA is the number of antigens which are present throughout ontogeny. Analysis of the conditions under which these two modes can coexist, shows that this is possible when a sufficiently numerous set of founder antigens couple in a tolerant mode, whereas isolated antigens first presented once development is completed couple in an immune response mode. The present model thus provides a possible mechanism for the distinction (hitherto purely descriptive) between a Central Immune System organized as a network and responsible for tolerance, and a Peripheral Immune System responsible for immune responses.