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, 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.
Okada
S
S
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Yoshida
T
T
Hong
Z
Z
Ishii
G
G
Hatano
M
M
Kuro-O
M
M
Nabeshima
Y
Y
Nabeshima
Y
Y
Tokuhisa
T
T
D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D015851:Interleukin-7 / Q000096:biosynthesis; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains
D015851:Interleukin-7