THE CHEMOKINE SDF-1, STROMAL CELL-DERIVED FACTOR-1, ATTRACTS EARLY-STAGE B-CELL PRECURSORS VIA THE CHEMOKINE RECEPTOR CXCR4

In the bone marrow progenitor (pro-) and precursor (pre-) B cells depe nd on close contact with stromal cells for growth and maturation Strom al cell-derived factor 1 (SDF-1), also known as pre-B cell growth-stim ulating factor, is produced by bone marrow stromal cells and was repor ted 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 di fferent typos of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220(+) bone marrow cells and several B cell lines chara cteristic for different stages of B lymphopoiesis, we now show that SD F-1 is a potent attractant for pro- and pre-B cells, but is inactive o n B cells at later stages of development. In early B cell precursors, SDF-1 induced intracellular Ca2+ mobilization and in vitro migration w ith a potency and efficacy similar to that observed for chemokines act ing on blood leukocytes. These responses were mediated via CXCR4 as th ey 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 crit ical hematopoietic function by selectively attracting and confining ea rly B cell precursors within the bone marrow microenvironment that pro vides the necessary factors for growth and differentiation.