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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Dynamics of memory B cells and plasmablasts in healthy individuals
Andrea Mazzolini1,2,3, Aleksandra M Walczak1, Thierry Mora1
1Laboratoire de physique de l'École normale supérieure, CNRS, Paris Sciences et Lettres University University, Sorbonne Université, Université Paris-Cité, Paris 75005, France.
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Our adaptive immune system relies on the persistence over long times of a diverse set of antigen-experienced B cells to encode our memories of past infections and to protect us against future ones. While longitudinal repertoire sequencing promises to track the long-term dynamics of many B cell clones simultaneously, sampling and experimental noise make it hard to draw reliable quantitative conclusions. Leveraging statistical inference, we infer the dynamics of memory B cell clonal dynamics and conversion to plasmablasts, which includes clone creation, degradation, abundance fluctuations, and differentiation. We find that memory B cell clones degrade slowly, with a half-life of 10 y. Based on the inferred parameters, we predict that it takes about 50 y to renew 50% of the repertoire, with most observed clones surviving for a lifetime. We infer that, on average, 1 out of 100 memory B cells differentiates into a plasmablast each year, more than expected from purely antigen-stimulated differentiation, and that plasmablast clones degrade with a half-life of about one year in the absence of memory imports. Our method is general and could be applied to other longitudinal repertoire sequencing B cell subsets.
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