Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells.
Bottom Line: In vitro and ex vivo methods, therefore, allow only limited understanding of the genuine immunobiology of FDCs in their native habitat.Herein, we used various multicolor fate mapping systems to investigate the ontogeny and dynamics of lymph node (LN) FDCs in situ.We further demonstrate that during an immune response, FDCs accumulate in germinal centers and that neither the recruitment of circulating progenitors nor the division of local mature FDCs significantly contributes to this accumulation.
Affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1104 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280 Marseille, France Aix-Marseille Univ (AMU), F-13284 Marseille, France.Show MeSH
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Mentions: As FDCs were not recruited from the circulation and did not divide in reactive follicles, we reasoned that they could originate from the local proliferation of CD21/35-negative FDC progenitors. According to this scenario, these progenitors would divide and give rise to daughter cells that would randomly acquire CFP or YFP expression upon CD21 expression. This postmitotic acquisition of colors would thus explain the absence of monocolored FDC foci observed in CD21Cre Ubow inflamed LNs. To unravel such a CD21/35− progenitor, we developed a third fate mapping system in which all stromal cells could undergo combinatorial recombination of the Ubow construct. RAG-2°/° Ubow+/+ mice were crossed to tamoxifen Cre-inducible Ubiquitin-Cre-ERT2 mice (Hayashi and McMahon, 2002; hereafter referred to as Ubow-CreERT2), irradiated, and reconstituted with WT BM cells. Reconstituted chimeras were treated with tamoxifen for 3 consecutive days and then maintained under a tamoxifen-free regimen for 1 wk to eliminate any remaining tamoxifen activity (Fig. S3). Mice were then injected with an emulsion of CFA/OVA in their ears and rear footpads (left side only). Inflamed (left) and control (right) auricular and popliteal LNs were harvested 3 wk later and stained for CD21/35 expression (Fig. 3). We reasoned that if CD21/35− FDC progenitors proliferated during that period, they should have generated foci of colored FDCs around them and thus unraveled their own localization in the follicle. Confocal analysis revealed that very few sparse FDCs in control follicles underwent recombination (Fig. 3 A). On the contrary, inflamed follicles were populated by nonrandomly distributed monocolored columnar foci of FDCs often connected to the subcapsular sinus (SCS; Fig. 3, B and C), indicative of local cell proliferation.
Affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2 Marseille, France Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 1104 Marseille, France Centre National de la Recherche Scientifique (CNRS), UMR7280 Marseille, France Aix-Marseille Univ (AMU), F-13284 Marseille, France.