Vondenhoff, M.F. et al. Separation of splenic red and white pulp occurs before birth in a LT-independent manner. J. Leukoc. Biol. 84, 152-161
For the formation of lymph nodes and Peyer's patches, lymphoid tissue inducer (LTi) cells are crucial in triggering stromal cells to recruit and retain hematopoietic cells. Although LTi cells have been observed in fetal spleen, not much is known about fetal spleen development and the role of LTi cells in this process. Here, we show that LTi cells collect in a periarteriolar manner in fetal spleen at the periphery of the white pulp anlagen. Expression of the homeostatic chemokines can be detected in stromal and endothelial cells, suggesting that LTi cells are attracted by these chemokines. As lymphotoxin (LT)alpha1beta2 can be detected on B cells but not LTi cells in neonatal spleen, starting at 4 days after birth, the earliest formation of the white pulp in fetal spleen occurs in a LTalpha1beta2-independent manner. The postnatal development of the splenic white pulp, involving the influx of T cells, depends on LTalpha1beta2 expressed by B cells.
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[Show abstract] [Hide abstract] ABSTRACT: Secondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5(+)Islet1(+) lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity.0Comments 16Citations
- "Once specified, splenic mesenchymal cells expand within the dorsal mesogastrium to form the splenic anlage (Brendolan et al., 2007). At midgestation, spleen mesenchymal cells include lymphoid tissue organizer (LTo) cells that are thought to be precursors for adult secondary lymphoid organ stromal cells (Katakai et al., 2008; Koning and Mebius, 2012; Mueller and Germain, 2009; Vondenhoff et al., 2008). Whether splenic LTo cells are capable of organizing the formation of lymphoid compartments and generating the different stromal cell subsets remains unknown. "
[Show abstract] [Hide abstract] ABSTRACT: The composition and function of stromal cells in the white pulp of the spleen resemble to a large extent the situation in other secondary lymphoid organs such as lymph nodes. The stromal cells play an important role in the support and guidance of lymphocytes and myeloid cells in the T and B cell zones of the spleen. Major differences of the spleen are found in the way cells enter the white pulp and the composition of stromal cells in the red pulp. In this review, the features of stromal cells of both white and red pulp will be described in light of the function of the spleen.0Comments 16Citations
- "Expression of homeostatic chemokines in stromal and endothelial cells suggests that LTi cells are attracted by these chemokines. As lymphotoxin-α1β2 can be detected on B cells but not on LTi cells in neonatal spleen, the earliest formation of the white pulp in fetal spleen occurs in an LTα1β2-independent manner (Vondenhoff et al., 2008). Although lymphotoxin signaling is not required for the formation of the white pulp and the segregation of red and white pulp, it is important for an optimal functional development of the lymphoid part of the spleen (Futterer et al., 1998). "
- [Show abstract] [Hide abstract] ABSTRACT: In this report we describe a transplantation system where embryonic spleens are grafted into adult hosts. This model can be used to analyze the cellular and molecular requirements for the development and organization of splenic microenvironments. Whole embryonic day 15 (ED15) spleens, grafted under the kidney capsule of adult mice, were colonized by host-derived lymphocytes and DC and developed normal splenic architecture. Grafts were also able to form germinal centers in response to T-dependent antigen. Using this system we demonstrated that adult host-derived lymphotoxin (LT) alpha was sufficient for the development of ED15 LT alpha(-/-) grafts. Grafting of ED15 LT alpha(-/-) spleens into RAG(-/-) hosts followed by transfer of LT alpha(-/-) splenocytes revealed no requirement for lymphocyte-derived LT alpha in the induction of CCL21 or the development of T-zone stroma. These data suggest that interactions between adult lymphoid-tissue inducer-like cells and embryonic stromal cells initiated T-zone development. Furthermore, adult lymphoid tissue inducer-like cells were shown to develop from bone marrow-derived progenitors. The model described here demonstrates a method of transferring whole splenic microenvironments and dissecting the stromal and hematopoietic signals involved in spleen development and organization.0Comments 12Citations
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