Transcriptional regulation of early B cell development.
All blood cell types including mature B cells derive from pluripotent hematopoietic stem cells. The developmental cues responsible for guiding multipotent cells to the B cell fate remain to be fully elucidated. During recent years, it has become clear that firm commitment to the B cell fate requires the active suppression of differentiation potentials for alternative fates. Through the work of our laboratory and many others, it is now apparent that early B cell development and B-lineage commitment is controlled by a complex interplay between specific cytokine receptors and a variety of transcription factors. Whereas the transcription factor Pax5 has been touted as the chief transcriptional regulator of B-lineage commitment, our recent studies suggest that the B cell fate is established through the concerted action of several transcription factors including Early B cell Factor-1 (EBF). Notably, we recently found that EBF is able to suppress myeloid and T cell differentiation when introduced into multipotent Pax5(null/null) progenitors. Past work has also established that EBF expression is connected to the activity of the receptor for the cytokine IL-7. Therefore, the IL-7/EBF pathway plays a key and non-redundant role in establishing the B cell fate. This work provides a provisional model for understanding the molecular basis for B cell developmental biology. Furthermore, because aging leads to a decline in early B cell development and reduced IL-7 responsiveness, this work establishes a conceptual framework for understanding how and why aging leads to the loss of early B cell precursors.
Northrup
Daniel L
DL
Department of Pathology and Laboratory Medicine, 230 John Morgan Building, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, Philadelphia, 19104-6082, PA, USA.
Allman
David
D
D000375:Aging / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D014157:Transcription Factors