The chemokine SDF‐1, stromal cell‐derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4

Jul 1, 1997European journal of immunology

The chemical SDF-1 attracts early B cell precursors through the receptor CXCR4

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Abstract

SDF-1 is a potent attractant for early B cell precursors in the bone marrow.

SDF-1 selectively attracts pro- and pre-B cells but is inactive on later-stage B cells.
In early B cell precursors, SDF-1 triggers intracellular calcium mobilization and migration.
These responses to SDF-1 are mediated via the CXCR4 receptor, which can be inhibited by specific antibodies.
Mice lacking SDF-1 experience severe B cell development deficiencies and die shortly after birth.
SDF-1 may play a critical role in retaining early B cell precursors in the bone marrow, supporting their growth and maturation.

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In the bone marrow, progenitor (pro-) and precursor (pre-) B cells depend on close contact with stromal cells for growth and maturation. Stromal cell-derived factor 1 (SDF-1), also known as pre-B cell growth-stimulating factor, is produced by bone marrow stromal cells and was reported 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 different types of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220+ bone marrow cells and several B cell lines characteristic for different stages of B lymphopoiesis, we now show that SDF-1 is a potent attractant for pro- and pre-B cells, but is inactive on B cells at later stages of development. In early B cell precursors, SDF-1 induced intracellular Ca2+ mobilization and in vitro migration with a potency and efficacy similar to that observed for chemokines acting on blood leukocytes. These responses were mediated via CXCR4 as they could be inhibited by an antireceptor 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 critical hematopoietic function by selectively attracting and confining early B cell precursors within the bone marrow microenvironment that provides the necessary factors for growth and differentiation.

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The chemokine SDF‐1, stromal cell‐derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4

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