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B220- bone marrow progenitor cells from New Zealand black autoimmune mice
exhibit an age-associated decline in Pre-B and B-cell generation
MS Merchant, BA Garvy and RL Riley
Department of Microbiology and Immunology, University of Miami School of
Medicine, FL 33101, USA.
New Zealand Black (NZB) autoimmune mice exhibit progressive, age- dependent
reduction in bone marrow pre-B cells. To ascertain the capacity of NZB bone
marrow B220- cells to generate pre-B cells in a supportive environment,
B-lineage (B220+) cell-depleted and T-cell- depleted bone marrow cells from
NZB mice at 1 to 3, 6, and 10 to 11 months of age were adoptively
transferred into irradiated (200R) C.B17 severe combined immunodeficient
(SCID) mice. Bone marrow pre-B cells (sIgM- CD43[S7]- B220+) were assessed
3 and 10 weeks posttransfer. Pre- B cells and B cells were reconstituted in
SCID recipients of older NZB progenitor cells by 10 weeks posttransplant,
in contrast to the very low numbers of pre-B cells present in the donor
bone marrow. However, B220- bone marrow progenitor cells from greater than
10-month-old NZB donors were deficient in the reconstitution of both pre-B
and B cells in SCID recipients at 3 weeks post-transfer. This reflected a
slower kinetics of repopulation, because older NZB-->SCID recipients had
numbers of both pre-B and B cells similar to recipients of young NZB
progenitor cells by 10 weeks posttransplant. Adoptive transfer of equal
mixtures of BALB/c and older NZB bone marrow B220- progenitor cells into
irradiated C.B17 SCID recipients failed to demonstrate active suppression.
These results suggest that, with age, NZB bone marrow has reduced numbers
and/or function of early B220- B-lineage progenitors. Consistent with this
hypothesis, B220- bone marrow cells from older NZB mice were deficient in
progenitors capable of yielding interleukin-7 (IL-7) responsive pre-B cells
in vitro on stimulation with the pre-B- cell potentiating factor,
insulin-like growth factor 1 (IGF-1).
Volume 85,
Issue 7,
pp. 1850-1857,
04/01/1995
Copyright © 1995 by The American Society of Hematology
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