Idiotypic networks: toward a renaissance?

Idiotypic networks, after being a dominating paradigm for more than a decade, have fallen out of fashion in parallel with the rapid success of molecular immunobiology. Today signs of a possible renaissance in idiotypic network studies are visible. For system biologists and also for physicists, the network idea remains attractive. Herein, a short account of the historical development of the paradigm is given. The necessary technical and conceptual ingredients for a theoretical description of idiotypic networks are briefly reviewed, and previous approaches are discussed. We also describe a minimalistic model developed in our group that allows for understanding the random evolution toward a highly non-trivial complex architecture. In the network, a connected large cluster of idiotype clones and many disconnected ones coexist, thus resembling the notion of central and peripheral parts proposed in the 'second-generation' version of the paradigm. The connected cluster consists of groups of idiotypic clones with clearly distinct statistical properties. The simplicity of the model allows for calculating the size of the groups and the number of inter- and intragroup links, which define the architecture. Aspects of idiotypic interactions in experimental medicine are discussed, along with the challenges to theory and experimentation.