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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 140-148
Heparan Sulfate Proteoglycans Mediate Interleukin-7- Dependent B
Lymphopoiesis
Lisa A. Borghesi,
Yoshio Yamashita, and
Paul W. Kincade
From the Oklahoma Medical Research Foundation, Immunobiology and
Cancer Program, Oklahoma City.
Heparin/heparan sulfate proteoglycans (HSPGs) have the potential to
bind and directly regulate the bioactivity of hematopoietic growth
factors including interleukin-7 (IL-7), a cytokine critical for murine
B-cell development. We examined the consequence of manipulating soluble
heparin and cell-surface heparan sulfate to IL-7-dependent responses
of B-cell precursors. Soluble heparin was found to inhibit production
of lymphoid, but not myeloid, cells in long-term bone marrow cultures.
Analysis of pro-B cells lacking plasma membrane HS suggests that this
glycosaminoglycan is required for efficient binding and responsiveness
to IL-7. By contrast, responses of hematopoietic cells to other
cytokines were not influenced by heparin addition or HS removal.
Therefore, HSPGs on B-lineage precursors may function as IL-7 receptor
components similar to HSPGs known to be important for the bFGF
receptor. Other experiments suggest that HSPGs on the surface of
stromal cells provide a weakly associating docking site for IL-7,
possibly controlling availability of this cytokine to B-cell
precursors. Together these data demonstrate a direct role for
heparinlike molecules in regulating the IL-7-dependent stages of
murine B lymphopoiesis.
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