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Mouse strain variability in the expression of the hematopoietic stem cell
antigen Ly-6A/E by bone marrow cells
GJ Spangrude and DM Brooks
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories,
National Institute of Allergy and Infectious Diseases, National Institutes
of Health, Hamilton, MT 59840.
The cell surface molecule Ly-6A/E provides a convenient marker for
primitive stem cells in the hematopoietic tissues of both fetal and adult
mice. However, previous studies have shown that Ly-6A/E expression by
lymphocytes is variable depending on the haplotype of the Ly-6 locus.
Therefore, strain-specific variation in Ly-6A/E expression by bone marrow
(BM) cells was investigated. The results show that Ly-6a mice have, on
average, 50% of the number of BM cells expressing Ly-6A/E relative to that
for Ly-6b mice. Furthermore, among the 5% of BM cells that do not express
antigens characteristic of mature T, B, myeloid, or erythroid lineages,
which include the primitive hematopoietic stem cell compartment, Ly-6a mice
have, on average, more than fivefold fewer Ly- 6A/E+ cells relative to that
for Ly-6b mice. Isolation of Ly-6A/E- and Ly-6A/E+ cells from mice of both
haplotypes showed that, whereas 99% of the marrow repopulating activity
(MRA) of C57BL/Ka (Ly-6b) mice could be recovered in the Ly-6A/E+ fraction,
only about 25% of the MRA of BALB/c (Ly-6a) was recoverable in the same
population. On a per-cell basis, the Ly-6A/E+ cells that were isolated from
BALB/c mice were essentially equivalent in MRA to those isolated from
C57BL/Ka mice. Thus, whereas a large percentage of the hematopoietic stem
cells of Ly- 6a mice do not express the Ly-6A/E molecule, the antigen may
be used to isolate a subset of stem cells from these mice. These results
show that hematopoietic stem cell phenotype can vary between mouse strains
and imply that caution should be exercised in the identification of human
stem cell antigens such as CD34, because a similar variability may occur
between individual humans. To further explore the influence of Ly- 6
haplotype on Ly-6A/E expression by specific cell subsets, lymph-node
lymphocytes from a panel of mouse strains were analyzed by multiparameter
flow cytometry for correlated expression of Ly-6A/E, CD4, and CD8. All
Ly-6a strains examined had less than 20% Ly-6A/E+ cells, and those cells
were predominantly CD8+ T lymphocytes. In contrast, the Ly-6b strains had
greater than 30% Ly-6A/E+ cells, and those cells included CD4+, CD8+, and B
lymphocytes.
Volume 82,
Issue 11,
pp. 3327-3332,
12/01/1993
Copyright © 1993 by The American Society of Hematology
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