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 Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-07-2085.

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Blood, 1 June 2003, Vol. 101, No. 11, pp. 4313-4321

HEMATOPOIESIS

In vitro identification of human pro-B cells that give rise to macrophages, natural killer cells, and T cells

Damien Reynaud, Nathalie Lefort, Elodie Manie, Laure Coulombel, and Yves Levy

From the Institut national de la santé et de la recherche médicale (INSERM) U474, Institut Cochin, Paris, France; Inserm U421, Créteil, France; Service d'immunologie clinique, Hôpital Henri Mondor, Créteil, France.

In this study we report the molecular and functional characterization of very early interleukin 7 receptor {alpha} (IL-7R{alpha})+-CD79a+CD19– B-cell progenitors, produced by human CD34+CD19–CD10– cord blood cells grown in the presence of stromal cells and cytokines. Purified IL-7R{alpha}+CD79a+CD19– cells transcribed the B-lymphoid specific genes E2A, EBF, TdT, Rag-1, had initiated DJH rearrangements, but almost lacked Pax-5 mRNA. When exposed to appropriate environmental conditions, these cells repressed B-cell genes and completely differentiated into CD14+ macrophages, CD56+ natural killer cells, and CD4high T cells. Retention of the DJH rearranged genes in both CD14+ and CD56+ cells unambiguously demonstrates that early B-cell genes, expressed prior to Pax-5, can be activated in a multipotent human progenitor cell whose final fate, including in non-B lineages, is determined by external signals.


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