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Individual CD34+CD38lowCD19-CD10- progenitor cells from human cord blood
generate B lymphocytes and granulocytes
AC Berardi, E Meffre, F Pflumio, A Katz, W Vainchenker, C Schiff and L Coulombel
INSERM U 362, Institut Gustave Roussy, Villejuif, France.
Identification of human hematopoietic stem cells and analysis of molecular
mechanisms regulating their function require biological assays that permit
differentiation in all hematopoietic lineages simultaneously. In this
study, we established conditions that permit the joint expression of the
B-lymphoid and myeloid potential from cord blood-derived
CD34+CD38lowCD19-/CD10- primitive progenitors that lack B- specific markers
and transcripts. When cocultured during 6 weeks with the murine stromal
cells MS-5 in the absence of exogenous human cytokines,
CD34+CD38low-CD19-CD10- cells generated a high number of CD19+ B cells.
Virtually all of these cells expressed a CD34-CD10+- CD19+cIgM- phenotype
of late pro-B cells and transcripts of Pax-5, lambda-like, and mu chain
were detected. We further show that 7% of CD34+CD38lowCD19- cells from cord
blood, when grown individually with MS-5 cells, generated both CD19+ and
CD11b+ cells after 6 weeks. Efficient B-cell differentiation was also
observed in vivo after transplantation of human cord blood-derived
unfractionated mononuclear cells or CD34+CD19+CD10- cells into
immune-deficient mice. In contrast to the in vitro situation, all stages of
B-cell differentiation were observed in vivo, including pro-B, pre-B, and
sIgM+ B cells. Interestingly, human progenitors with the ability to
differentiate along both B-lymphoid and granulocytic pathways were also
detected among human CD34+CD38low cells in the marrow of chimeric mice 6 to
7 weeks after transplantation. Both in vitro and in vivo systems will offer
an invaluable tool to further identify the lymphoid and myeloid
potentialities of primitive progenitor cells isolated from fetal as well as
adult human hematopoietic tissues and characterize stromal- derived signals
that regulate their function.
Volume 89,
Issue 10,
pp. 3554-3564,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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