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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Self assertion modeled as a network repertoire of multi-determinant antibodies
1Department of Theoretical Biology, Utrecht University, The Netherlands. takumi@binf.biol.ruu.nl,rdb@alive.biol.ruu.nl
Abstract:
We study repertoire selection in a network of natural antibodies that is maintained by stimulatory idiotypic interactions. The natural antibody repertoire develops in an environment of self epitopes to which the self-reactive B cell clones are completely tolerant. For the modeling formalism, we extend the shape space framework so that each antibody is represented by several randomly chosen shapes. B cell clones are generated stochastically and are removed whenever their density falls below an extinction threshold. The idiotypic interactions are governed by a log bell-shaped interaction function. The natural antibody repertoire in the model is formed by percolation: the network is autonomously activated following a point stimulation. Our main conclusion is that the natural antibody repertoire organizes itself in such a way that most self epitopes are included in the repertoire. We find an over-representation of antibody determinants that are similar to self epitopes. We speculate that the network forms a "smoke screen" covering the somatic self.
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