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Abstract: The population dynamics theory of B cells in a typical germinal center couldplay an important role in revealing how affinity maturation is achieved.However, the existing models encountered some conflicts with experiments. Toresolve these conflicts, we present a coarse-grained model to calculate the Bcell population development in affinity maturation, which allows acomprehensive analysis of its parameter space to look for optimal values ofmutation rate, selection strength, and initial antibody-antigen binding levelthat maximize the affinity improvement. With these optimized parameters, themodel is compatible with the experimental observations such as the ~100-foldaffinity improvements, the number of mutations, the hypermutation rate, and the-all or none- phenomenon. Moreover, we study the reasons behind the optimalparameters. The optimal mutation rate, in agreement with the hypermutation ratein vivo, results from a tradeoff between accumulating enough beneficialmutations and avoiding too many deleterious or lethal mutations. The optimalselection strength evolves as a balance between the need for affinityimprovement and the requirement to pass the population bottleneck. Thesefindings point to the conclusion that germinal centers have been optimized byevolution to generate strong affinity antibodies effectively and rapidly. Inaddition, we study the enhancement of affinity improvement due to B cellmigration between germinal centers. These results could enhance ourunderstandings to the functions of germinal centers.



Autor: Jingshan Zhang, Eugene I. Shakhnovich

Fuente: https://arxiv.org/



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