Researchers used computational simulations and experiments to investigate how genetic variations encoded in the germline impact B-cell responses.
By Dr. Chinta SidharthanAug 29 2023Reviewed by Sophia Coveney In a recent study published in the journal PLOS Pathogens, researchers used computational simulations and experiments with murine models to investigate how genetic variations encoded in the germline impact B-cell responses and understand variations in individual responses to vaccines and infections.
The sequence of amino acids in the B-cell receptor region determines the affinity of the B-cell receptor for an antigen, and is therefore, dependent on the germline recombination of the genes that code for immunoglobulins, and the somatic mutations that occur in these genes within the lifetime of an individual.
They carried out computational simulations where the size of the advantages encoded by the germline variations relative to the effect size variation and rate of somatic mutations determined the similarities in allele usage in different individuals. If the use of a specific allele results in higher initial affinity for the antigen or the affinity developed through affinity maturation is higher for some lineages than others, the allele would have ratio of a greater than one across individuals.
Relative to the somatic mutations, if the advantage offered by the germline alleles was greater, the B-cell responses across individuals were dominated by B-cells with specific alleles. However, if the advantages due to germline variations were weaker, the B-cell responses across individuals would vary according to the somatic mutations over time, despite the similarities in the initial responses.
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