SDF-1 responsiveness does not correlate with CXCR4 expression levels of developing human bone marrow B cells.
Chemokines and their receptors are broadly expressed in different tissues and are involved in diverse biologic processes. Gene inactivation studies have shown that both stromal cell derived factor-1 (SDF-1) and chemokine receptor 4 (CXCR4) are essential for B lymphopoiesis. However, it is not yet clear by which mechanisms B lymphopoiesis is affected. In the present study, we have examined CXCR4 expression and function on primary B cells representing sequential stages of development (eg, pro-B, pre-B, immature, and mature B cells) in fetal and adult bone marrow. The expression of CXCR4 was observed to be sinusoidal. Expression was highest on pre-B cells, decreased as cells developed into immature B cells, and then increased again upon transition to the mature B-cell stage. The corresponding ligand SDF-1 was shown to trigger vigorous cell signaling and migration responses, which are restricted to early lineage B cells. The responsiveness to SDF-1 was markedly decreased for immature and mature B cells despite relatively high levels of CXCR4 expression. Thus, the diminished responsiveness to SDF-1 by more mature B cells was determined to be disproportionate to the level of CXCR4 expression. These findings raise the possibility that CXCR4 function is differentially controlled during B lymphopoiesis and may be relevant to the compartmentalization of B-cell precursors in the bone marrow.
Honczarenko
M
M
Division of Hematology-Oncology, the Departments of Pathology and Laboratory Medicine and Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Douglas
R S
RS
Mathias
C
C
Lee
B
B
Ratajczak
M Z
MZ
Silberstein
L E
LE
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D019718:Receptors, CXCR4 / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4