The aging of early B-cell precursors

Allman, David
Miller, Juli P.

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Correspondence to: David Allman, PhD, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, 269 John Morgan Building, Philadelphia, PA 19104-6082, USA. Tel.: +1 215 746 5547; Fax: +1 215 573 2350; E-mail: [email protected]

Acknowledgements: We thank Dr Jean Labriola Scholz for critically reviewing this manuscript. We, in addition, thank our long-time collaborators Drs Michael Cancro and Avinash Bhandoola. D. A. is the recipient of a Career Development Program Award from the Leukemia and Lymphoma Society.

Immunological Reviews 205(1):p 18-29, June 2005.

Summary

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.