Impairment of B lymphopoiesis in precocious aging (klotha) mice

Seiji Okada, Toru Yoshida, Zhang Hong, Genichiro Ishii, Masahiko Hatano, Makoto Kuro-O, Yoko Nabeshima, Yo Ichi Nabeshima, Takeshi Tokuhisa

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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. The kl/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.

Original languageEnglish (US)
Pages (from-to)861-871
Number of pages11
JournalInternational Immunology
Issue number6
StatePublished - 2000


  • Hematopoiesis
  • IL-7
  • Microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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