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 journalArticle

45 Citations (Scopus)

Abstract

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
Volume12
Issue number6
StatePublished - 2000

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Lymphopoiesis
Interleukin-7
B-Lymphocytes
Bone Marrow
Erythroid Cells
Lymphopenia
B-Lymphoid Precursor Cells
Interleukin-3
Hematopoiesis
Gene Silencing
Myeloid Cells
Hematopoietic Stem Cells
Bone Marrow Cells
Atrophy
Stem Cells
Spleen
Phenotype
Gene Expression
Polymerase Chain Reaction
Injections

Keywords

  • Hematopoiesis
  • IL-7
  • Microenvironment

ASJC Scopus subject areas

  • Immunology

Cite this

Okada, S., Yoshida, T., Hong, Z., Ishii, G., Hatano, M., Kuro-O, M., ... Tokuhisa, T. (2000). Impairment of B lymphopoiesis in precocious aging (klotha) mice. International Immunology, 12(6), 861-871.

Impairment of B lymphopoiesis in precocious aging (klotha) mice. / Okada, Seiji; Yoshida, Toru; Hong, Zhang; Ishii, Genichiro; Hatano, Masahiko; Kuro-O, Makoto; Nabeshima, Yoko; Nabeshima, Yo Ichi; Tokuhisa, Takeshi.

In: International Immunology, Vol. 12, No. 6, 2000, p. 861-871.

Research output: Contribution to journalArticle

Okada, S, Yoshida, T, Hong, Z, Ishii, G, Hatano, M, Kuro-O, M, Nabeshima, Y, Nabeshima, YI & Tokuhisa, T 2000, 'Impairment of B lymphopoiesis in precocious aging (klotha) mice', International Immunology, vol. 12, no. 6, pp. 861-871.
Okada S, Yoshida T, Hong Z, Ishii G, Hatano M, Kuro-O M et al. Impairment of B lymphopoiesis in precocious aging (klotha) mice. International Immunology. 2000;12(6):861-871.
Okada, Seiji ; Yoshida, Toru ; Hong, Zhang ; Ishii, Genichiro ; Hatano, Masahiko ; Kuro-O, Makoto ; Nabeshima, Yoko ; Nabeshima, Yo Ichi ; Tokuhisa, Takeshi. / Impairment of B lymphopoiesis in precocious aging (klotha) mice. In: International Immunology. 2000 ; Vol. 12, No. 6. pp. 861-871.
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