Determination of lymphoid cell fate is dependent on the expression status of the IL-7 receptor.
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.
Purohit
Sheetal J
SJ
Department of Microbiology and Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA.
Stephan
Robert P
RP
Kim
Hyung-Gyoon
HG
Herrin
Brantley R
BR
Gartland
Larry
L
Klug
Christopher A
CA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000276:immunology; D005472:Fluorouracil / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051757:PAX5 Transcription Factor; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics*; D014184:Transplantation, Homologous / Q000276:immunology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D020395:Receptors, Interleukin-7; D014157:Transcription Factors; D005472:Fluorouracil