Transplantation of embryonic spleen tissue reveals a role for adult non-lymphoid cells in initiating lymphoid tissue organization.
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.
Glanville
Stephanie H
SH
MRC Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham, UK.
Bekiaris
Vasileios
V
Jenkinson
Eric J
EJ
Lane
Peter J L
PJ
Anderson
Graham
G
Withers
David R
DR
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D054421:Chemokine CCL21 / Q000378:metabolism; D007668:Kidney / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D013154:Spleen / Q000166:cytology / Q000196:embryology* / Q000276:immunology* / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology*
D000957:Antigens, Viral, Tumor; D054421:Chemokine CCL21; D008233:Lymphotoxin-alpha