Haematopoietic stem cells in spleen have distinct differentiative potential for antigen presenting cells

Abstract

Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice and to give rise to L-DC, as well as other splenic APC. Neonatal spleen cells were transplanted into allotype-distinct lethally irradiated hosts along with host-type competitor BM cells, and assayed over 8 to 51 weeks for haematopoietic reconstitution of L-DC and cDC subsets, along with other lymphoid and myeloid cells. In this study, neonatal spleen showed multilineage haematopoietic reconstitution in mouse chimeras, rather than specific or restricted ability to differentiate into L-DC. However, the representation of individual APC subsets was found to be unequal in chimeras partially reconstituted with donor cells, such that more donor-derived progeny were seen for L-DC than for myeloid and cDC subsets. The ability of HSC in spleen to develop into L-DC was indicated by a strong bias in the subset size of these cells over other splenic APC subsets. This type of evidence supports a model whereby spleen represents an important site for haematopoiesis of this distinct DC subset. The conditions under which haematopoiesis of L-DC occurs in spleen, or the progenitors involved, will require further investigation.