Abstract
SUMMARYFollicular 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.
Highlights
The ability to mount effective humoral immune responses throughout life is critical for normal antibody-mediated protection and healthy aging (Gibson et al, 2009; Frasca et al, 2011)
B cells are generated in the bone marrow (BM) and enter the spleen where they complete development as transitional cells, characterized by the induction of CD23 and immunoglobulin D (IgD), together with downregulation of IgM and AA4.1 (Allman et al, 2001; Loder et al, 1999)
Follicular mature (FM) B cells recirculate between lymph nodes (LNs) and spleen, where cognate encounter with antigen triggers activation and the development of germinal center (GC) reactions
Summary
Verheijen and Rane et al combine fate mapping and mathematical models to quantify the development and dynamics of follicular mature B cells and germinal center B cells in spleen and lymph nodes, and show how these processes vary across the mouse lifespan. Highlights d Follicular mature B cells are a homogeneous population that self-renews infrequently d Host environment drives cell-extrinsic, age-related changes in B cell homeostasis d Clones in naturally occurring germinal centers (GC) persist for weeks with rapid turnover d GC B cells in spleen and lymph nodes have different precursors and distinct dynamics. November 17, 2020 a 2020 The Authors.
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