Age-dependent abnormalities of hematopoietic stem cells in (NZW x BXSB)F-1mice

The (NZW x BXSB)F-1 (W/BF1) mouse is known as an autoimmune-prone strain wh ich develops lupus nephritis, thrombocytopenia due to platelet-specific aut oantibodies, leukocytosis, and myocardial infarction. In this experiment, w e investigated the age dependent abnormalities of the hematopoietic stem ce lls (HSCs) and hematopoiesis in this mouse. White blood cell counts (especi ally Mac-1- or Gr-1-positive cells) in the peripheral blood of 12-week-old W/BF1 mice increased in comparison with those of four-week-old W/BF1 or nor mal mice. To investigate whether the abnormal hematopoiesis can be attribut ed to the HSCs of W/BF1 mice, colony-forming unit in spleen (CFU-S) and col ony-forming unit in culture (CFU-C) assays were performed. Day 12 CFU-S cou nts of 12-week-old W/BF1 mice significantly increased in comparison with th ose of four-week-old W/BF1 mice or normal mice. In the CFUC assay, CFU-GEMM and CFU-GM counts in 12-week-old W/BF1 mice increased in comparison with t hose of four-week-old W/BF1 or control mice. The bone marrow cells (BMCs) f rom 12-week-old W/BF1 mice showed a high level of G-CSF and a low level of GM-CSF in mRNA expression. To examine the effect of HSCs from 12-week-old W /BF1 mice on the onset of autoimmune diseases and the abnormal hematopoiesi s, T- and B-cell-depleted BMCs of four-week-old or 12-week-old W/BF1 mice w ere transplanted to C3H mice. Recipient C3H mice that had received the BMCs from 12-week-old W/BF1 mice showed an earlier onset of autoimmune diseases and a shorter survival rate than those that had received the BMCs from fou r-week-old W/BF1 mice. These data suggest that the HSCs from 12-week-old W/ BF1 mice showing the symptoms of autoimmune diseases have the capacity to i nduce autoimmune diseases earlier than the HSCs from four-week-old W/BF1 mi ce.