Maturation decreases responsiveness of human bone marrow B lineage cells to stromal-derived factor 1 (SDF-1)

We compared the chemotactic responsiveness of different subsets of human B lineage cells to stromal derived factor-1 (SDF-1), High percentages (30-40% of input) of purified bone marrow progenitors including non-B lineage prog enitors, pro-B cells, and pre-B cells migrated to SDF-1 alpha, demonstratin g that SDF-1 is an efficacious chemoattractant of these cells, Pro-B cells responded optimally to a lower concentration of SDF-1 than other subsets, d emonstrating that SDF-I is a more potent chemoattractant of this subset. A lower percentage (10-15% of input) of mature B lymphocytes migrated to SDF- 1 alpha than pro-B cells, demonstrating that responsiveness of B lineage ce lls to SDF-1 decreases during differentiation. Inhibition by anti-CXCR4 mAb demonstrated that migration of B lineage cells to SDF-1 was completely dep endent on CXC chemokine receptor-P (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro-B cells, de spite differences in responsiveness to SDF-1, CXCR4 receptors expressed by unresponsive and SDF-1-responsive B cells bound SDF-1 alpha with similar af finities (K-D = 1.7-3.3 X 10(-9) M), Therefore, elements downstream from CX CR4 appear to regulate responsiveness of B cells to SDF-1, We speculate tha t SDF-1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis.