Lymphoid development from hematopoietic stem cells.

Mechanisms and pathways for commitment to the lymphoid lineage from hematopoietic stem cells (HSC) remain controversial. The interleukin-7 receptor (IL-7R) transduces nonredundant signals for both T- and B-cell development. Recently, we identified a clonogenic common lymphoid progenitor population in mouse bone marrow that can give rise to T, B, and natural killer (NK) cells, but lacks myeloid differentiation capacity. These cells are not self-renewing stem cells, but progenitors that have a limited life span. HSC do not express IL-7R, and the upregulation of the IL-7R occurs at the stage of common lymphoid progenitors. The IL-7R mediates nonredundant signals to reinforce the survival of developing T cells, and to promote rearrangement of immunoglobulin heavy chain genes in B-cell progenitors. Thus, common lymphoid progenitors exist in early hematopoiesis, and expression of the IL-7R is a critical step in the initiation of lymphoid development from HSC.