Expression of the IL-7 receptor alpha (IL-7R) is a distinguishing feature of common lymphoid progenitors (CLP) in mice. Human B cell development has been thought to differ from that in mouse with respect to the requirement for IL-7. Our previous studies show that IL-7 plays a critical role in human B cell production (J Immunol. 2009, 182:4255). Here we use IL-7R expression to identify a human CLP population that can be generated from hematopoietic stem cells (HSCs) in umbilical cord blood (CB). Following two weeks of co-culture with primary human bone marrow (BM) stroma, CB CD34+ cells give rise to a CD34+CD19-IL-7R+ progenitor population that is absent from fresh, uncultured CB. IL-7R+ progenitors make up ~17% of the CD19-CD34+ cells present in culture at 2 weeks. A similar IL-7R+ human progenitor population is generated in the BM of immunodeficient mice following transplant with human CD34+ CB cells. FACS-sorted CD34+CD19-IL-7R+ progenitors produced in co-culture or in the human-mouse xenograft model give rise to CD19+ B cells and CD56+ NK cells in bulk and single cell culture, but lack myeloid potential in CFU assays and when transplanted into immunodeficient mice. Ongoing experiments will evaluate the T lineage potential of IL-7R+ progenitors in the human-mouse xenograft model. These data will be important for developing therapies to accelerate and enhance lymphoid reconstitution from HSCs in CB, a hematopoietic source used increasingly for stem cell transplant.
- Copyright © 2011 by The American Association of Immunologists, Inc.