Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice

Adult bone marrow is a major site for hematopoiesis, and reduction of the b one marrow cavity induces hematopoiesis in extramarrow tissues. To Investig ate the rudimentary intramarrow and the compensatory extramarrow hematopoie sis, particularly B lymphopoiesis, we used 3 osteopetrotic mouse strains [o p/op, mi/ mi, and Fos (-/-)], which are severely deficient in functional os teoclasts and therefore form Inadequate bone marrow cavities, We found that bone marrow in these osteopetrotic mice supports myelopoiesis but not B ly mphopoiesis, although cells that have the potential to differentiate into B lineage cells are present in the bone marrow. Although B lymphopoiesis nor mally occurs both in the spleen and liver of newborn mice, compensatory B l ymphopoiesis in adult op/op and mi/mi mice is observed only in the liver, w hile myelopoiesis is enhanced in both organs. Interestingly, mice lacking t he Fos proto-oncogene exhibit B lymphopoiesis in the spleen as well as live r. The amounts of expression of steel factor, Flt3/Flk-2 ligand, and interl eukin-7 in the bone marrow, spleen, or liver were not significantly affecte d in these osteopetrotic mutants. These findings suggest that the volume of the bone marrow cavity regulates B lymphopoiesis without affecting the pro duction of certain hematopoietic growth factors. The splenic microenvironme nts that support both myelopoiesis and B lymphopoiesis in the neonatal stag e are lost in adults and are not reactivated even in the osteopetrotic adul ts unless the Fos gene is disrupted, (Blood, 2000;95:3363-3370) (C) 2000 by The American Society of nematology.