Age‐Dependent Abnormalities of Hematopoietic Stem Cells in (NZW × BXSB)F 1 Mice

The (NZW × BXSB)F 1 (W/BF 1 ) mouse is known as an autoimmune‐prone strain which develops lupus nephritis, thrombocytopenia due to platelet‐specific autoantibodies, leukocytosis, and myocardial infarction. In this experiment, we investigated the age‐dependent abnormalities of the hematopoietic stem cells (HSCs) and hematopoiesis in this mouse. White blood cell counts (especially Mac‐1‐ or Gr‐1‐positive cells) in the peripheral blood of 12‐week‐old W/BF 1 mice increased in comparison with those of four‐week‐old W/BF 1 or normal mice. To investigate whether the abnormal hematopoiesis can be attributed to the HSCs of W/BF 1 mice, colony‐forming unit in spleen (CFU‐S) and colony‐forming unit in culture (CFU‐C) assays were performed. Day 12 CFU‐S counts of 12‐week‐old W/BF 1 mice significantly increased in comparison with those of four‐week‐old W/BF 1 mice or normal mice. In the CFU‐C assay, CFU‐GEMM and CFU‐GM counts in 12‐week‐old W/BF 1 mice increased in comparison with those of four‐week‐old W/BF 1 or control mice. The bone marrow cells (BMCs) from 12‐week‐old W/BF 1 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/BF 1 mice on the onset of autoimmune diseases and the abnormal hematopoiesis, T‐ and B‐cell‐depleted BMCs of four‐week‐old or 12‐week‐old W/BF 1 mice were transplanted to C3H mice. Recipient C3H mice that had received the BMCs from 12‐week‐old W/BF 1 mice showed an earlier onset of autoimmune diseases and a shorter survival rate than those that had received the BMCs from four‐week‐old W/BF 1 mice. These data suggest that the HSCs from 12‐week‐old W/BF 1 mice showing the symptoms of autoimmune diseases have the capacity to induce autoimmune diseases earlier than the HSCs from four‐week‐old W/BF 1 mice.