Enhanced precursor B cell apoptosis in the bone marrow of CSF-1-deficient OP/OP mice

Abstract

Osteopetrotic (op/op) mice are deficient in macrophages and osteoclasts due to a CSF-1 gene mutation. This study aimed to evaluate the effect of these deficiencies and of CSF-1-dependent mechanisms on B lymphopoiesis in bone marrow. B cell development and apoptoses have been examined in bone marrow of op/op mice, using immuno-fluorescence labeling and flow cytometry. 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 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 B lineage cells. The findings provide evidence that CSF-1-dependent mechanisms can strongly influence the survival of precursor B cells in mouse bone marrow. 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.