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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3363-3370
Intramedullary and extramedullary B lymphopoiesis in osteopetrotic
mice
Hisashi Tagaya,
Takahiro Kunisada,
Hidetoshi Yamazaki,
Toshiyuki Yamane,
Takeshi Tokuhisa,
Erwin F. Wagner,
Tetsuo Sudo,
Leonard D. Shultz, and
Shin-Ichi Hayashi
From the Department of Immunology, School of Life Science, Faculty
of Medicine, Tottori University, Yonago, Tottori, Japan; Division of
Developmental Genetics, Chiba University Graduate School of Medicine,
Chiba, Japan; Research Institute of Molecular Pathology, Vienna,
Austria; Basic Research Laboratories, Toray Industries, Inc, Kamakura,
Kanagawa, Japan; and Jackson Laboratory, Bar Harbor, ME.
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.
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