Impairment of B lymphopoiesis in precocious aging (klotho) mice

Inactivation of the klotho gene in mice results in multiple disorders that resemble human aging after 3 weeks of age, Because hematopoiesis, especiall y B lymphopoiesis, is affected in humans and mice by aging, we analyzed the hematopoietic state in homozygous klotho (kl/kl) mice, The kl/kl mice show ed thymic atrophy and a reduced number of splenocytes. These mice had almos t the normal number of myeloid cells, erythroid cells, IL-3-responsive myel oid precursors and colony forming units in spleen (CFU-S) in bone marrow (B M), but had a substantially decreased number of B cells in BM and periphera l blood as compared with wild-type mice, IL-7-responsive B cell precursors and all of the maturation stages of B cells in BM were also reduced, Howeve r, the function of hematopoietic stem cells including their capacity of B l ymphopoiesis in vivo and in vitro was normal. Early B cell development was also normal in neonates and young kl/kl mice until 2 weeks old without agin g phenotypes, RT-PCR analysis revealed that the level of IL-7 gene expressi on was significantly reduced in freshly isolated kl/kl BM cells. However, i njection of IL-7 in kl/kl mice could not rescue the B lymphopenia, These fi ndings indicate that Klotho protein may regulate B lymphopoiesis via its in fluence on the hematopoietic microenvironment.