Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice.
Document Type
Article
Publication Date
2000
Keywords
Animal, B-Lymphocytes, Bone-Marrow-Cells, Genes-fos, Hematopoiesis, Hematopoietic-Stem-Cells, Heterozygote, Homozygote, Interleukin-7, Liver, Mice, Mice-Inbred-C57BL, Mice-Knockout, Osteopetrosis, Polymerase-Chain-Reaction, Proto-Oncogene-Proteins, Proto-Oncogene-Proteins-c-fos, Receptor-Protein-Tyrosine-Kinases, Spleen, Stem-Cell-Factor, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S
First Page
3363
Last Page
3370
JAX Source
Blood 2000 Jun; 95(11):3363-70.
Grant
CA20408/CA/NCI
Abstract
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.
Recommended Citation
Tagaya H,
Kunisada T,
Yamazaki H,
Yamane T,
Tokuhisa T,
Wagner EF,
Sudo T,
Shultz LD,
Hayashi SI.
Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice. Blood 2000 Jun; 95(11):3363-70.