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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2578-2586. Prepublished online as a Blood First Edition Paper on July 6, 2006; DOI 10.1182/blood-2005-12-010827.
Submitted December 1, 2005
Centre de Therapie Cellulaire et Genique, Institut Paoli-Calmettes, France * Corresponding author; email: imbertam{at}marseille.fnclcc.fr.
Haematopoietic progenitor cell trafficking is an important phenomenon throughout life. It is thought to occur in sequential steps, similarly to what has been described for mature leukocytes. Molecular actors have been identified for each step of leukocyte migration: recently, CD99 was shown to play a part during trans-endothelial migration. We explored the expression and role of CD99 on human haematopoietic progenitors. We demonstrate that i) CD34+ cells express CD99, albeit with various intensities, ii) subsets of CD34+ cells with high or low levels of CD99 expression produce different numbers of erythroid, NK or dendritic cells in in vitro differentiation assays, iii) the level of CD99 expression is related to the ability to differentiate towards B cells, iv) CD34+ cells that migrate through an endothelial monolayer in response to SDF-1a and SCF display the highest level of CD99 expression, v) binding of a neutralizing antibody to CD99 partially inhibits trans-endothelial migration of CD34+ progenitors in an in vitro assay, vi) binding of a neutralizing antibody to CD99 reduces homing of CD34+ progenitors xeno-transplanted in NOD-SCID mice. We conclude that expression of CD99 on human CD34+ progenitors has functional significance, and that CD99 may be involved in trans-endothelial migration of progenitors.
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