International Immunology, Vol. 12, No. 6, 861-871,
June 2000
© 2000 Japanese Society for Immunology
Impairment of B lymphopoiesis in precocious aging (klotho) mice
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
1 Department of Pathology and Tumor Biology, Graduate School of Medicine, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
2 First Department of Pathology, Chiba University School of Medicine, Chiba 260-8670, Japan
3 Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9072, USA
4 Division of Molecular Genetics, National Institute of Neuroscience, NCNP, Kodaira 187-8502, Japan
5 Core Research for Evolutional Science and Technology (CREST), JRDC, Tokyo, Japan
Correspondence to: T. Tokuhisa
Inactivation of the klotho gene in mice results in multiple disorders that resemble human aging after 3 weeks of age. Because hematopoiesis, especially B lymphopoiesis, is affected in humans and mice by aging, we analyzed the hematopoietic state in homozygous klotho (kl/kl) mice. Thekl/kl mice showed thymic atrophy and a reduced number of splenocytes. These mice had almost the normal number of myeloid cells, erythroid cells, IL-3-responsive myeloid precursors and colony forming units in spleen (CFU-S) in bone marrow (BM), but had a substantially decreased number of B cells in BM and peripheral 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. However, the function of hematopoietic stem cells including their capacity of B lymphopoiesis 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 aging phenotypes. RT-PCR analysis revealed that the level of IL-7 gene expression was significantly reduced in freshly isolated kl/kl BM cells. However, injection of IL-7 in kl/kl mice could not rescue the B lymphopenia. These findings indicate that Klotho protein may regulate B lymphopoiesis via its influence on the hematopoietic microenvironment.
Keywords: hematopoiesis, IL-7, microenvironment
Transmitting editor: C. J. Paige
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