Unique progenitors in adult mouse bone marrow expressing CD127 (IL-7Rα) and high level of cKit efficiently develop into all lymphocytes including T cells and innate lymphoid cells (HEM2P.266)

Abstract

Abstract All lymphocytes are thought to develop from common lymphoid progenitors (CLPs) that are found in the Lin−Sca-1locKitloCD127+Flt3hi bone marrow (BM) cell population. However, only small numbers of T cells and innate lymphoid cells (ILCs) are generated from CLPs transplanted into irradiated mice, suggesting that they might mainly develop from alternative progenitors such as lymphoid-primed multipotent progenitors (LMPPs). We now have identified novel progenitors in adult mouse BM that efficiently develop into all lymphocytes including T cells and ILC2s. The novel progenitors are similar to LMPPs and found in the cKithiSca-1+Flt3+ BM cell subset, but unlike LMPPs they express the lymphoid lineage marker CD127, thus resembling early thymic progenitors (ETPs). Upon transplantation into irradiated mice, CD127+ LMPP-like cells robustly engraft and develop into T, B, NK cells and ILC2s. They are more efficient than LMPPs and CLPs in generating T cells and ILC2s. Similar to LMPPs, they also retain myeloid potentials. Flt3L-deficient mice have greatly reduced LMPPs and CLPs but have almost normal numbers of CD127+ LMPP-like progenitors, pre-ILC2 in the BM and mature ILC2 in the lung. While the exact relationship between CD127+ LMPP-like progenitors, CD127- LMPPs and CLPs are yet to be clarified, these results suggest that CD127+ LMPP-like BM cells are important progenitors for T cells and ILC2s independent of CLPs.