The chemokine SDF‐1, stromal cell‐derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4

Abstract

In the bone marrow, progenitor (pro‐) and precursor (pre‐) B cells depend on close contact with stromal cells for growth and maturation. Stromal cell‐derived factor 1 (SDF‐1), also known as pre‐B cell growth‐stimulating factor, is produced by bone marrow stromal cells and was reported to act together with interleukin‐7 as co‐mitogen for pre‐B cells. SDF‐1 was recently shown to be a chemokine which is chemotactic for different types of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220+ bone marrow cells and several B cell lines characteristic for different stages of B lymphopoiesis, we now show that SDF‐1 is a potent attractant for pro‐ and pre‐B cells, but is inactive on B cells at later stages of development. In early B cell precursors, SDF‐1 induced intracellular Ca 2+ mobilization and in vitro migration with a potency and efficacy similar to that observed for chemokines acting on blood leukocytes. These responses were mediated via CXCR4 as they could be inhibited by an anti‐receptor antibody. SDF‐1 is the first chemokine shown to act on early‐stage B cell precursors. Mice lacking SDF‐1 die perinatally and show a severe deficiency in B lymphopoiesis. We propose that SDF‐1 released from the stromal cells exerts its critical hematopoietic function by selectively attracting and confining early B cell precursors within the bone marrow microenvironment that provides the necessary factors for growth and differentiation.