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) α was sufficient for the development of ED15 LTα−/− grafts. Grafting of ED15 LTα−/− spleens into RAG−/− hosts followed by transfer of LT α−/− splenocytes revealed no requirement for lymphocyte-derived LT α 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.
Highlights
The generation of efficient immune responses to T-dependent Ag requires organization and segregation of the B- and T-cell populations within secondary lymphoid tissue [1,2,3]
Hematopoietic cells within the graft were mostly of host origin including B cells, both CD41 and CD81 T cells and CD11c1 DC (Fig. 1B and C). These cells were distributed into T-zone areas with associated B-cell follicles, surrounded by an IgM1IgDÀ marginal zone (Fig. 2A and Supporting Information Fig. 1). Consistent with this organization, expression of CCL21 was detected within the T zone and CXCL13 was expressed within the follicular areas
We have previously described the presence of cells within adult secondary lymphoid tissue with a phenotype matching that of lymphoid tissue inducer (LTi) [27]
Summary
The generation of efficient immune responses to T-dependent Ag requires organization and segregation of the B- and T-cell populations within secondary lymphoid tissue [1,2,3]. CD30 has been identified in the segregation of splenic B and T cells, the mechanism remains unclear [11] During both LN and PP development, lymphoid tissue inducer (LTi) cells, a population of CD451CD3ÀCD11cÀB220ÀCD41 IL-7Ra1 cells that express LTa1b2 and a4b1 [12,13,14,15,16,17] cluster with VCAM-11ICAM-11 stromal cells that express LTb-R. Engagement of the RET ligand, ARTN, expressed by gut stromal cells is proposed as a mechanism through which LTi are recruited to the sites of PP formation Whether these cells and the RET/ARTN signaling pathway are involved in the formation of other secondary lymphoid tissue is unclear
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