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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 2990-2998
SDF-1 Responsiveness Does Not Correlate With CXCR4 Expression
Levels of Developing Human Bone Marrow B Cells
Marek Honczarenko,
Raymond S. Douglas,
Clarissa Mathias,
Benhur Lee,
Mariusz Z. Ratajczak, and
Leslie E. Silberstein
From the Division of Hematology-Oncology, the Departments of
Pathology and Laboratory Medicine and Medicine, University of
Pennsylvania School of Medicine, Philadelphia, PA.
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.
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