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How affinity influences tolerance in an idiotypic network

par Hart, Emma;Bersini, Hugues ;Santos, Francisco C.
Référence Journal of theoretical biology, 249, 3, page (422-436)
Publication Publié, 2007-12

Article révisé par les pairs

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Résumé :

Idiotypic network models give one possible justification for the appearance of tolerance for a certain category of cells while maintaining immunization for the others. In this paper, we provide new evidence that the manner in which affinity is defined in an idiotypic network model imposes a definite topology on the connectivity of the potential idiotypic network that can emerge. The resulting topology is responsible for very different qualitative behaviour of the network. We show that using a 2D shape-space model with affinity based on complementary regions, a cluster-free topology results that clearly divides the space into distinct zones; if antigens fall into a zone in which there are no available antibodies to bind to, they are tolerated. On the other hand, if they fall into a zone in which there are highly concentrated antibodies available for binding, then they will be eliminated. On the contrary, using a 2D shape space with an affinity function based on cell similarity, a highly clustered topology emerges in which there is no separation of the space into isolated tolerant and non-tolerant zones. Using a bit-string shape space, both similar and complementary affinity measures also result in highly clustered networks. In the networks whose topologies exhibit high clustering, the tolerant and intolerant zones are so intertwined that the networks either reject all antigen or tolerate all antigen. We show that the distribution and topology of the antibody network defined by the complete set of nodes and links-an autonomous feature of the system-therefore selects which antigens are tolerated and which are eliminated. © 2007 Elsevier Ltd. All rights reserved.