Precursor B Cells from Pax-5-deficient mice — Stem Cells for Macrophages, Granulocytes, Osteoclasts, Dendritic Cells, Natural Killer Cells, Thymocytes and T Cells

Abstract

At least three major cell differentiation lineages cooperate to build the system of lymphoid organs, each one derived from a separate stem cell. Hematopoietic stem cells give rise to T-lymphoid cells in the thymus and to B-lymphoid and myeloid cells in the bone marrow. Fibroblastic and epithelial stem cells seed the bone marrow and thymus to provide the stromal cell environment in bone marrow, and the cortical and medullary epithelial cell layers in the thymus. Interactions between the fibroblasts and epithelial cells on the one side and the hematopoietic cells on the other induce both lineages to their differentiation pathways, and organize different regions in the primary lymphoid organs — fetal liver, thymus, bone marrow — as much as they do so in the secondary lymphoid organs, such as spleen and lymph nodes. Finally, endothelial cells form the vessels through and between lymphoid organs which allow hematopoietic cells in a process of attachment and transmigration to enter the vessels, migrate in them from one site through blood and lymph, and exit into another site. The formation of bone needs yet another cell lineage to generate osteoblasts which build bone (Rodan and Harada 1997), in balance with the osteolytic osteoclasts which are provided by hematopoietic stem cells.