Apoptosis and its modulation during B lymphopoiesis in mouse bone marrow.
Studies in normal, gene-deleted, transgenic and mutant mice have examined apoptotic cell death and its role in B lymphopoiesis in bone marrow. Apoptotic activity has been quantitated among phenotypically defined populations of precursor B cells using flow cytometry of apoptotic cells and an established model of B-cell development. In normal mice, the frequencies of apoptotic cells (apoptotic index) and accumulation of apoptotic cells during short-term culture (apoptotic rate) are maximal at around the pro/pre-B-cell transition and among immature B lymphocytes. The brief period between onset of apoptosis and clearance by macrophages (apoptotic transit time) is similar for most precursor B-cells. Apoptosis-modulating factors produce substantial changes in apoptotic activity among pro-B and pre-B cells, associated with altered expression of bcl-2 family proteins. Pro-B-cell apoptosis, normally extensive, is markedly suppressed in the absence of p53. Complete pro-B-cell abortion in RAG-2 deletion provides an assay for apoptotic fractions in other experimental systems. Pre-B-cell apoptosis is enhanced by deficiencies of interleukin (IL)-7, Abl protooncogene or colony-stimulating factor (CSF)-1 and overexpression of heat-stable antigen, and is inhibited by IL-7 and p190bcr/abl transgenes. CSF-1 and melatonin administration inhibit pre-B-cell apoptosis, probably via stromal cell stimulation. Such apoptotic modulation has implications for B-cell homeostasis, quality control, immunodeficiency and neoplasia.
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D051927:CD24 Antigen; D002454:Cell Differentiation; D019070:Cell Lineage; D003115:Colony-Stimulating Factors / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D006706:Homeostasis; D015851:Interleukin-7 / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
D015703:Antigens, CD; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D003115:Colony-Stimulating Factors; D004268:DNA-Binding Proteins; D015851:Interleukin-7; D008562:Membrane Glycoproteins; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D016159:Tumor Suppressor Protein p53; C064655:V(D)J recombination activating protein 2; D016315:Proto-Oncogene Proteins c-abl