Novel mouse NK progenitors in lymph node: developmental origin and functional contributions. (138.1)

Abstract

Abstract Natural killer (NK) cells are widely distributed in various tissues. Among them, lymph node (LN) NK cells have been shown to differ from spleen NK cells in their phenotype and function. About ~20% of LN NK cells have rearranged TCRγ genes, express CD127+ (IL-7Rα), and they are thought to derive from the thymus. However, LN NK cells from nude mice are normal in number and phenotype, suggesting that the majority of LN NK cells are thymus-independent. We have recently found a novel cell population in the LN of C57/BL6 mice that is lineage (LIN)-negative but expresses the pan NK cell marker CD49b (DX5). LIN-CD49b+ cells are also found in the bone marrow (BM), but they differ from the LN counterparts. BM LIN-CD49b+ cells are Sca-1locKithiCD127- and include common lymphoid progenitors and other immature hematopoietic progenitors whereas LN LIN-CD49b+ cells are Sca-1+cKit-CD127+. When cultured on OP9 stroma cells, LN LIN-CD49b+ cells acquire the NK cells markers NK1.1, CD122 and Ly49 as well as cytotoxic function and IFN-γ production. They also retain CD127 expression. The precursor frequency of NK progenitors among LIN- CD49b+ cells in LN and BM are 1/40 and 1/13, respectively. Thus, LN LIN- CD49b+ cells seem to represent a novel NK progenitor that migrates from the BM to the LN for final differentiation into unique subsets of mature NK cells. This work is supported by a grant from the German Research Council (DFG) and the National Cancer Institute of Canada.