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Fate Mapping Quantifies the Dynamics of B Cell Development and Activation throughout Life

Verheijen, M; Rane, S; Pearson, C; Yates, AJ; Seddon, B; (2020) Fate Mapping Quantifies the Dynamics of B Cell Development and Activation throughout Life. Cell Reports , 33 (7) , Article 108376. 10.1016/j.celrep.2020.108376. Green open access

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Abstract

Follicular mature (FM) and germinal center (GC) B cells underpin humoral immunity, but the dynamics of their generation and maintenance are not clearly defined. Here, we exploited a fate-mapping system in mice that tracks B cells as they develop into peripheral subsets, together with a cell division fate reporter mouse and mathematical models. We find that FM cells are kinetically homogeneous, recirculate freely, are continually replenished from transitional populations, and self-renew rarely. In contrast, GC B cell lineages persist for weeks with rapid turnover and site-specific dynamics. Those in the spleen derive from transitional cells and are kinetically homogeneous, while those in lymph nodes derive from FM B cells and comprise both transient and persistent clones. These differences likely derive from the nature of antigen exposure at the different sites. Our integrative approach also reveals how the host environment drives cell-extrinsic, age-related changes in B cell homeostasis.

Type: Article
Title: Fate Mapping Quantifies the Dynamics of B Cell Development and Activation throughout Life
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2020.108376
Publisher version: http://dx.doi.org/10.1016/j.celrep.2020.108376
Language: English
Additional information: © 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: B cells, mathematical modeling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10115650
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