B-cell deficiency and reduced B-cell reconstitution in hemoglobin-deficit mice.
OBJECTIVE
To study the effect of persistent hemoglobin-deficit mutation (hbd/hbd) on hematopoiesis and the function of hematopoietic stem cells (HSCs).


METHODS
Young and old mice homozygous for the spontaneous hbd/hbd mutation were compared to young and old wild-type control mice, all on the C57BL/6 background, over cellular composition in blood and bone marrow (BM) using cell counting, complete blood counts, and flow cytometry. BM cells from hbd/hbd mutants and normal controls were also tested for HSC engraftment in vivo using the competitive repopulation assay.


RESULTS
Both young and old hbd/hbd mutants exhibited a microcytic anemia with significantly (p<0.01) lower levels of hemoglobin and mean corpuscular volume. There were significant declines in CD45R+ B cells in both blood (p<0.01) and BM (p<0.05) in old hbd/hbd mice, suggesting that B-cell homeostasis was compromised. Total BM cells per mouse was significantly increased (p<0.05) in old hbd/hbd mice. In the competitive repopulation assay in vivo, BM cells from old hbd/hbd donors showed slightly decreased contribution to T cells and myeloid cells but a significantly (p<0.01) decreased engraftment in B lymphocytes, indicating that B-cell hematopoiesis was compromised in old hbd/hbd mice. These data differ from results previously obtained from normal C57BL/6 mice in which BM cell engraftment ability does not decrease with donor age.


CONCLUSIONS
Persistent hbd/hbd mutation causes hematopoiesis defects in the B cell lineage.
Lipovsky
Karen
K
Hematology Branch, National Heart, Lung, and Blood Institute/NIH, Building 10 Room 7C118, 9000 Rockville Pike, Bethesda, MD 20892-1652, USA.
Bennett
Lori A
LA
Chen
Jichun
J
D000367:Age Factors; D000740:Anemia / Q000235:genetics / Q000628:therapy; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D001773:Blood Cells / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D006085:Graft Survival / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006454:Hemoglobins / Q000172:deficiency* / Q000235:genetics; D007970:Leukopenia / Q000235:genetics*; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation
D006454:Hemoglobins