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Publication : Regulation of cell survival during B lymphopoiesis in mouse bone marrow: enhanced pre-B-cell apoptosis in CSF-1-deficient op/op mutant mice.

First Author  Lu L Year  2001
Journal  Exp Hematol Volume  29
Issue  5 Pages  596-601
PubMed ID  11376872 Mgi Jnum  J:69425
Mgi Id  MGI:1934556 Doi  10.1016/s0301-472x(01)00621-x
Citation  Lu L, et al. (2001) Regulation of cell survival during B lymphopoiesis in mouse bone marrow: enhanced pre-B-cell apoptosis in CSF-1-deficient op/op mutant mice. Exp Hematol 29(5):596-601
abstractText  OBJECTIVE: Osteopetrotic (op/op) mice are deficient in macrophages and osteoclasts due to a CSF-1 gene mutation. The aim of this study was to evaluate the effect of these deficiencies and of CSF-1-dependent mechanisms on B lymphopoiesis in bone marrow, with special reference to the apoptotic activity of precursor B cells. MATERIALS AND METHODS: B-cell development and apoptosis were examined in the bone marrow of op/op mice using immunofluorescence labeling and flow cytometry. Short-term cultures of bone marrow were used to evaluate the effect of recombinant CSF-1 on the rate of B-cell apoptosis. RESULTS: Bone marrow cellularity was greatly reduced in op/op mice compared with normal littermates. However, precursor B cells were disproportionately decreased, most markedly at the pre-B-cell stage. Precursor B cells, particularly pre-B cells, displayed elevated apoptotic incidences both ex vivo and in short-term culture. Addition of recombinant CSF-1 reduced the incidence of apoptosis among precursor B cells in short-term cultures of whole bone marrow suspensions from normal mice but not in cultures of sorted B220+ B-lineage cells. CONCLUSIONS: The finding of increased pre-B-cell apoptosis in op/op mice provides evidence that CSF-1-dependent mechanisms can strongly influence the survival of precursor B cells in mouse bone marrow, particularly at the pro-B/pre-B cell transition. It is proposed that the local or systemic levels of CSF-1 during ontogeny may thus play a role in regulating B-cell production within the bone marrow microenvironment.
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