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


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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Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Osmond
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D019070:Cell Lineage; D002478:Cells, Cultured / Q000187:drug effects; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000473:pathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor