In vitro identification of human pro-B cells that give rise to macrophages, natural killer cells, and T cells.
In this study we report the molecular and functional characterization of very early interleukin 7 receptor alpha (IL-7Ralpha)+-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-7Ralpha+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.
Reynaud
Damien
D
Institut national de la santé et de la recherche médicale (INSERM), Paris, France.
Lefort
Nathalie
N
Manie
Elodie
E
Coulombel
Laure
L
Levy
Yves
Y
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology; D019891:Leukopoiesis / Q000235:genetics*; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000032:analysis; D017154:Stromal Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology
D015703:Antigens, CD; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain