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Maturation decreases responsiveness of human bone marrow B lineage cells to stromal‐derived factor 1 (SDF‐1)
Author(s) -
Fedyk Eric R.,
Ryan Daniel H.,
Ritterman Ion,
Springer Timothy A.
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.4.667
Subject(s) - stromal cell , biology , bone marrow , lineage (genetic) , human bone , immunology , microbiology and biotechnology , cancer research , genetics , gene , in vitro
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 progenitors, pro‐B cells, and pre‐B cells migrated to SDF‐1α, demonstrating 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, demonstrating that SDF‐1 is a more potent chemoattractant of this subset. A lower percentage (10–15% of input) of mature B lymphocytes migrated to SDF‐1α than pro‐B cells, demonstrating that responsiveness of B lineage cells to SDF‐1 decreases during differentiation. Inhibition by anti‐CXCR4 mAb demonstrated that migration of B lineage cells to SDF‐1 was completely dependent on CXC chemokine receptor‐4 (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro‐B cells, despite differences in responsiveness to SDF‐1. CXCR4 receptors expressed by unresponsive and SDF‐1‐responsive B cells bound SDF‐1a with similar affinities ( K D = 1.7–3.3 × 10 −9 M). Therefore, elements downstream from CXCR4 appear to regulate responsiveness of B cells to SDF‐1. We speculate that SDF‐1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis. J. Leukoc. Biol. 66: 667–673; 1999.