Random walks on binary strings applied to the somatic hypermutation of B-cells

DOI10.1016/J.MBS.2018.03.022zbMATH Open1392.92022arXiv1501.07806OpenAlexW2963966353WikidataQ52627013 ScholiaQ52627013MaRDI QIDQ1644684FDOQ1644684

Authors: Irene Balelli, Vuk Milišić, Gilles Wainrib 

Publication date: 22 June 2018

Published in: Mathematical Biosciences (Search for Journal in Brave)

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.

Full work available at URL: https://arxiv.org/abs/1501.07806

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zbMATH Keywords

hypercubehitting timerandom walks on graphssomatic hypermutationevolutionary landscapemutational model

Mathematics Subject Classification ID

Random walks on graphs (05C81) Cell biology (92C37)

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Cited In (7)

• Arcsine laws for random walks generated from random permutations with applications to genomics
• Mathematical modeling of lymphocytes selection in the germinal center
• A branching stochastic evolutionary model of the B-cell repertoire
• Random walks on binary strings applied to the somatic hypermutation of B-cells
• Analyzing different variants of immune inspired somatic contiguous hypermutations
• Multi-type Galton-Watson processes with affinity-dependent selection applied to antibody affinity maturation
• Title not available (Why is that?)

Uses Software

• SimRank

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