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 LN MRCs reside below the SCS, we analyzed the outer follicle of inflamed LNs harvested from CD21Cre Ubow+/+ chimeras. Confocal pictures indicated that CD21/35− RANK-Lhi dTomato+ CFPneg YFPneg MRCs formed a cellular layer below the SCS of reactive follicles (Fig. 5 A). Interestingly, a discrete population of maturing CD21/35+ RANK-Lmed dTomatomed CFPmed (or YFPmed) FDCs was immediately juxtaposed to this MRC layer and contiguous to the more central population of mature CD21/35+ RANK-Lneg dTomatoneg CFPhi (or YFPhi) FDCs. As LN FDCs cannot be efficiently isolated from nonirradiated LNs, we next quantified the colors and numbers of MRCs and transitional and mature FDCs on tissue sections. The great majority of CD21/35− RANK-L+ MRCs expressed dTomato in the absence of YFP or CFP while almost all mature CD21/35+ RANK-L− FDCs expressed YFP or CFP in absence of dTomato (Fig. 5 C). Interestingly, 77% of CD21/35+ RANK-L+ cells (172 out of 223 cells) coexpressed dTomato and YFP or CFP, confirming their transitional stage between MRCs and mature FDCs. In addition, these transitional cells represented 1.9% of all RANK-L+ cells (30 out of 1,514 cells) in control LNs while they represented 16.6% of all RANK-L+ cells (323 out of 1,935 cells) in inflamed LNs, suggesting that such transition was increased in reactive follicles. To rule out the contribution of an unknown follicular cell type to the generation of FDCs, we also analyzed the colors of all RANK-L− CD21/35− fluorescent cells present in the follicles of these mice. These data show that the majority of these cells expressed dTomato while very few of them coexpressed dTomato and YFP (or CFP), confirming that the transitional phenotype was almost exclusively observed in MRCs and FDCs. Further analysis indicated that dTomato+ RANK-L+ MRCs expressed CXCL13 but did not display the pre-FDC markers NG2 and Mfge-8 (Krautler et al., 2012; not depicted), supporting the recent evidence that splenic and LN FDC progenitors are of different origins (Castagnaro et al., 2013). These results indicate that MRCs give rise to FDCs during inflammation-induced remodeling of B cell follicles.
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.