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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-02-0653.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3672-3680
IMMUNOBIOLOGY
Relationships between early B- and NK-lineage lymphocyte
precursors in bone marrow
Taku Kouro,
Vinay Kumar, and
Paul W. Kincade
From the Immunobiology and Cancer Program, Oklahoma
Medical Research Foundation, Oklahoma City; and the Department of
Pathology, University of Chicago, IL.
Recent studies have demonstrated that lineage marker-negative
(Lin ) c-kitLo Flk-2/Flt3+
IL-7R+ Sca-1Lo CD27+
Ly-6C Thy-1CD43+
CD16/32Lo/ terminal deoxynucleotidyl transferase
(TdT)+ cells in murine bone marrow are functional
lymphocyte precursors. However, it has not been clear if this is an
obligate intermediate step for transit of multipotential hematopoietic
stem cells to natural killer (NK) cells. We have now used serum-free,
stromal cell-free cultures to determine that NK progenitors are
enriched among an estrogen-regulated, c-kitLo subset of the
Lin fraction. However, several experimental approaches
suggested that this population is heterogeneous and likely represents a stage where B and NK lineages diverge. Although most B-cell precursors were directly sensitive to estrogen in culture, much of the NK-cell precursor activity in that fraction was hormone resistant. B-lineage potential was largely associated with interleukin 7 receptor  (IL-7R) expression and was selectively driven in culture by IL-7. In
contrast, many NK precursors did not display detectable amounts of this
receptor and their maturation was selectively supported by IL-15.
Finally, single-cell experiments showed that the Lin
c-kitLo fraction contains a mixture of B/NK, B-restricted,
and NK-restricted progenitors. Two-step culture experiments revealed
that NK precursors become hormone resistant on or before acquisition of
CD122, signaling commitment to the NK lineage. CD45R is preferentially,
but not exclusively, expressed on maturing B-lineage cells. Production of these 2 blood cell types is regulated in bone marrow by common and
then independent mechanisms that can now be studied with greater precision.
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