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Generation of Lymph Node-fat Pad Chimeras for the Study of Lymph Node Stromal Cell Origin
Published on: December 16, 2013
Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells
Meryem Jarjour1, Audrey Jorquera1, Isabelle Mondor1
1Centre 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.
Insights
Follicular dendritic cells (FDCs) form networks in lymph nodes from marginal reticular cells (MRCs). MRCs also generate new FDCs during immune responses, revealing their crucial role in FDC biology.
Area of Science:
- Immunology
- Cell Biology
- Lymphoid Organ Development
Background:
- Follicular dendritic cells (FDCs) are crucial for B cell function and antibody responses.
- Their in vivo biology and ontogeny remain poorly understood due to limitations of in vitro/ex vivo studies.
- FDCs form intricate networks within secondary lymphoid organs like lymph nodes.
Purpose of the Study:
- To investigate the in situ ontogeny and dynamics of lymph node (LN) FDCs.
- To identify the cellular origins and expansion mechanisms of FDCs during immune responses.
- To elucidate the role of marginal reticular cells (MRCs) in FDC biology.
Main Methods:
- Utilized multicolor fate mapping systems in mice.
- Performed in situ analysis of lymph node cellular dynamics.
- Investigated FDC accumulation during immune responses.
Main Results:
- LN FDC networks originate from clonal expansion and differentiation of MRCs.
- MRCs are lymphoid stromal cells located along the LN subcapsular sinus.
- During immune responses, FDC accumulation is primarily driven by new FDC generation from MRCs, not circulating progenitors or mature FDC division.
Conclusions:
- Marginal reticular cells (MRCs) are the primary source for both the initial formation and the expansion of FDC networks in lymph nodes.
- This study identifies a critical, previously underappreciated function for MRCs in orchestrating FDC populations.
- Understanding FDC ontogeny from MRCs provides insights into adaptive immunity and germinal center regulation.
Abstract:
Follicular dendritic cells (FDCs) regulate B cell function and development of high affinity antibody responses but little is known about their biology. FDCs associate in intricate cellular networks within secondary lymphoid organs. 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 show that LN FDC networks arise from the clonal expansion and differentiation of marginal reticular cells (MRCs), a population of lymphoid stromal cells lining the LN subcapsular sinus. 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. Rather, we provide evidence that newly generated FDCs also arise from the proliferation and differentiation of MRCs, thus unraveling a critical function of this poorly defined stromal cell population.

