Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice.
Adult bone marrow is a major site for hematopoiesis, and reduction of the bone marrow cavity induces hematopoiesis in extramarrow tissues. To investigate the rudimentary intramarrow and the compensatory extramarrow hematopoiesis, particularly B lymphopoiesis, we used 3 osteopetrotic mouse strains [op/op, mi/mi, and Fos (-/-)], which are severely deficient in functional osteoclasts and therefore form inadequate bone marrow cavities. We found that bone marrow in these osteopetrotic mice supports myelopoiesis but not B lymphopoiesis, although cells that have the potential to differentiate into B lineage cells are present in the bone marrow. Although B lymphopoiesis normally occurs both in the spleen and liver of newborn mice, compensatory B lymphopoiesis in adult op/op and mi/mi mice is observed only in the liver, while myelopoiesis is enhanced in both organs. Interestingly, mice lacking the Fos proto-oncogene exhibit B lymphopoiesis in the spleen as well as liver. The amounts of expression of steel factor, Flt3/Flk-2 ligand, and interleukin-7 in the bone marrow, spleen, or liver were not significantly affected in these osteopetrotic mutants. These findings suggest that the volume of the bone marrow cavity regulates B lymphopoiesis without affecting the production of certain hematopoietic growth factors. The splenic microenvironments that support both myelopoiesis and B lymphopoiesis in the neonatal stage are lost in adults and are not reactivated even in the osteopetrotic adults unless the Fos gene is disrupted.
Tagaya
H
H
Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Kunisada
T
T
Yamazaki
H
H
Yamane
T
T
Tokuhisa
T
T
Wagner
E F
EF
Sudo
T
T
Shultz
L D
LD
Hayashi
S I
SI
D000375:Aging; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D016762:Genes, fos; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D015851:Interleukin-7 / Q000235:genetics; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010022:Osteopetrosis / Q000235:genetics / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013154:Spleen / Q000276:immunology; D019089:Stem Cell Factor / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3
D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D019089:Stem Cell Factor; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3