The chemokine CXCL12 and regulation of HSC and B lymphocyte development in the bone marrow niche.

Chemokines are a family of small structurally related molecules that were recognized originally for their ability to regulate cell trafficking in inflammation. We have found that a chemokine, CXC chemokine ligand 12/stromal cell-derived factor/pre-B-cell growth stimulating factor (CXCL12/ SDF-1/PBSF) and its physiologic receptor CXCR4 are essential for hematopoiesis including B lymphocyte development and colonization of bone marrow by hematopoietic cells including hematopoietic stem cells (HSCs) during ontogeny as well as cardiovascular formation. Recently, we have shown that a small population of reticular stromal cells, which has high levels of CXCL 12 expression, termed CXCL 2-abundant reticular (CAR) cells have several long processes and are scattered throughout adult bone marrow. In addition, most of the earliest B cell precursors, pre-pro-B cells and end-stage B cells, plasma cells, which require CXCL12, as well as primitive hematopoietic progenitors were attached to the CAR cells. These results suggest that the CAR cells function as cellular niches for B-cell development and that CXCL12 plays a role in maintaining the blood cells in the niches. It has been hypothesized that osteoprogenitors reside in the stromal tissues of bone marrow and play an important role in hematopoiesis. The nature and functions of CAR cells are important issues for the future.