title: The aging of early B-cell precursors.
abstract: B-cell genesis in the bone marrow declines with advancing age. In this review, we discuss our current understanding of why B-cell production rates decline with age with a special emphasis on why age-related factors might target very early lymphoid precursors. We consider the impact of aging on cytokine responsiveness and how current models for lineage relationships for very early B- and T-cell precursors might influence interpretations of experiments addressing age-associated declines in B- and T-cell differentiation. This discussion centers on the notion that aging affects events associated with the process by which hematopoietic stem cells are guided toward the B-cell pathway. Finally, we present a model in which the age-associated loss of early B-cell precursors is linked to suboptimal function of key transcriptional regulators of very early B-cell development.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA. dallman@mail.med.upenn.edu
authors.forename: David
authors.initials: D
authors.lastname: Allman
authors.forename: Juli P
authors.initials: JP
authors.lastname: Miller
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D016922:Cellular Senescence; D006801:Humans; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism