B220- bone marrow progenitor cells from New Zealand black autoimmune mice exhibit an age-associated decline in Pre-B and B-cell generation.
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).
Merchant
M S
MS
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA.
Garvy
B A
BA
Riley
R L
RL
D000375:Aging / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology*; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002452:Cell Count; D003114:Colony-Forming Units Assay; D005260:Female; D006085:Graft Survival; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D016219:Immunotherapy, Adoptive; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB / Q000033:anatomy & histology / Q000254:growth & development / Q000276:immunology*; D016513:Mice, SCID; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000473:pathology
D000954:Antigens, Surface; D015851:Interleukin-7; D007334:Insulin-Like Growth Factor I; D017493:Leukocyte Common Antigens