Apoptosis and macrophage-mediated cell deletion in the regulation of B lymphopoiesis in mouse bone marrow.
Studies of cell population dynamics and microenvironmental organization of B lymphopoiesis in the bone marrow of normal mice and in various genetically modified states have shown that cell loss, involving processes of apoptosis and macrophage-mediated cell deletion, is a prominent feature of the primary genesis of B lymphocytes. Balanced against the influence of proliferative stimulants, the programmed death of precursor B cells provides a quantitative control, determining the magnitude of the final output of functional B lymphocytes to the peripheral immune system. The cell loss mechanisms can be readily set in motion by external or systemic influences, making the B-cell output particularly vulnerable to suppression by ionizing irradiation, stress or other systemic mediators. In addition, however, cell loss exerts an important quality control in the formation of the primary B-cell repertoire. The combination of apoptosis and macrophage-mediated deletion, acting at successive stages of B-cell differentiation, efficiently eliminates many precursors having non-productive Ig gene rearrangements, cell cycle dysregulations, and certain autoreactive Ig specificities. Outstanding areas of further work abound. Important questions concern the nature of mechanisms which underlie the processes of B-cell apoptosis and macrophage deletion in bone marrow, the microenvironmental signals involved in B-cell life or death decisions and genetic factors which may override these B-cell culling mechanisms. The answers will be relevant to problems of autoimmune disease, humoral immunodeficiency and B-cell neoplasia.
Osmond
D G
DG
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Rico-Vargas
S
S
Valenzona
H
H
Fauteux
L
L
Liu
L
L
Janani
R
R
Lu
L
L
Jacobsen
K
K
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology*; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000276:immunology; D008264:Macrophages / Q000502:physiology*; D051379:Mice