A MODEL OF THE IMMUNE NETWORK WITH B-T CELL COOPERATION .2. THE SIMULATION OF ONTOGENY

This paper is based on a new model of the immune network which explici tly incorporates B-T cell co-operation. A major feature of this model is the simplifying assumption that inhibition by anti-TCR soluble Ig i s the only possible down-regulatory influence on activated T-cells. Th is model is capable of coupling with antigens in both an ''immune resp onse'' 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 i dentify the conditions under which each of these modes of antigen coup ling occurs. Achieving the tolerant mode depends principally on four p arameters: a high value of S-B, the rate of bone-marrow production of B-cells; a relatively high efficiency of T-help through mIg-TCR recogn ition compared with (MHC + peptide)-TCR interaction; and a relatively high value of the product P-R.N-A, where P-R is the average probabilit y that an Ig recognizes another molecule and N-A is the number of anti gens 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 toler ant mode, whereas isolated antigens first presented once development i s completed couple in an immune response mode. The present model thus provides a possible mechanism for the distinction thitherto purely des criptive) between a Central Immune System organized as a network and r esponsible for tolerance, and a Peripheral Immune System responsible f or immune responses.