A MODEL OF THE IMMUNE NETWORK WITH B-T CELL COOPERATION .1. PROTOTYPICAL STRUCTURES AND DYNAMICS

Hitherto, ''second generation'' network models of the immune system ha ve all been restricted to B-lymphocytes and the Ig molecules they prod uce. These models have not so far been able to provide a convincing me chanism for the distinction between a ''Central Immune System'' (CIS) composed of a connected network of lymphocyte clones which couple with ''self'' antigens in a tolerant mode, and a ''Peripheral Immune Syste m'' (PIS) composed of clones with little or no supra-clonal organizati on and which produce classical immune responses when interacting with ''non-self'' antigens. Here, we present a new network model which expl icitly incorporates B-T cell co-operation. In this model, B-cell. acti vation is dependent on T-cell help, and activated T-cells are down-reg ulated by engagement of their TCRs by soluble Ig. We discuss the under lying biology on which we base the system of ordinary differential equ ations which defines the present network model. We then illustrate som e basic features of the model by examining several prototypical situat ions with a small number of clones. Depending on the idiotypic connect ivity structure, the model exhibits two distinct modes of coupling wit h antigens: an ''immune response'' mode in which T- and B-cell clones grow exponentially; and a ''tolerant'' mode in which T-cell clones are controlled by inclusion of all TCRs in the repertoire of an idiotypic B-cell network. Finally, we discuss the simplifying assumptions of th e present model and argue that its range of validity is indeed the reg ion of the state-space of the system where the discrimination between the CIS and the PIS takes place. (C) 1996 Elsevier Science Limited