Journal
EMBO JOURNAL
Volume 22, Issue 20, Pages 5511-5521Publisher
OXFORD UNIV PRESS
DOI: 10.1093/emboj/cdg522
Keywords
B cell commitment; EBF; IL-7 receptor; Pax5; T cell development
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Funding
- NIAID NIH HHS [AI T32 07051] Funding Source: Medline
- NIDDK NIH HHS [R01DK54766] Funding Source: Medline
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Signaling through the IL-7 receptor (IL-7R) is necessary for the development of the earliest B- and T-lineage cells. IL-7R is first expressed on common lymphoid progenitor cells and is not detected on primitive common myeloid progenitors. In this study, we show that enforced expression of IL-7R on multipotential stem cells does not influence lymphoid versus myeloid cell fate. T cell development was compatible with sustained IL-7R expression; however, we observed a near complete block in B cell development at the onset of B-lineage commitment. Unlike pre-proB cells from control animals, developmentally-arrested IL-7R(+)B220(+)CD19(-)NK1.1(-)Ly-6C(-) cells failed to express EBF and Pax5. These results suggest that transient downregulation of IL-7R signaling is a necessary event for induction of EBF and Pax5 expression and B-lymphocyte commitment.
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