The aging of early B-cell precursors

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.