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 oste oclasts due to a CSF-I gene mutation. The aim of this study was to evaluate the effect of these deficiencies and of CSF-l-dependent mechanisms on B Ly mphopoiesis in bone marrow, with special reference to the apoptotic activit y of precursor B cells. Materials and Methods. B-cell development and apoptosis were examined in th e bone marrow of op/op mice using immunofluorescence labeling and flow cyto metry, Short-term cultures of bone marrow were used to evaluate the effect of recombinant CSF-I 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 disproportionatel y decreased, most markedly at the pre-B-cell stage. Precursor B cells, part icularly pre-B cells, displayed elevated apoptotic incidences both ex vivo and in short-term culture, Addition of recombinant CSF-I reduced the incide nce of apoptosis among precursor B cells in short-term cultures of whole bo ne 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 pr ovides evidence that CSF-l-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 producti on within the bone marrow microenvironment, (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.