Random walks on binary strings applied to the somatic hypermutation of B-cells
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Abstract: Within the germinal center in follicles, B-cells proliferate, mutate and differentiate, while being submitted to a powerful selection~: a micro-evolutionary mechanism at the heart of adaptive immunity. A new foreign pathogen is confronted to our immune system, the mutation mechanism that allows B-cells to adapt to it is called {em somatic hypermutation}~: a programmed process of mutation affecting B-cell receptors at extremely high rate. By considering random walks on graphs, we introduce and analyze a simplified mathematical model in order to understand this extremely efficient learning process. The structure of the graph reflects the choice of the mutation rule. We focus on the impact of this choice on typical time-scales of the graphs' exploration. We derive explicit formulas to evaluate the expected hitting time to cover a given Hamming distance on the graphs under consideration. This characterizes the efficiency of these processes in driving antibody affinity maturation. In a further step we present a biologically more involved model and discuss its numerical outputs within our mathematical framework. We provide as well limitations and possible extensions of our approach.
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- Random walks on binary strings applied to the somatic hypermutation of B-cells
Cited in
(7)- Analyzing different variants of immune inspired somatic contiguous hypermutations
- scientific article; zbMATH DE number 3867103 (Why is no real title available?)
- Mathematical modeling of lymphocytes selection in the germinal center
- Multi-type Galton-Watson processes with affinity-dependent selection applied to antibody affinity maturation
- A branching stochastic evolutionary model of the B-cell repertoire
- Random walks on binary strings applied to the somatic hypermutation of B-cells
- Arcsine laws for random walks generated from random permutations with applications to genomics
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