Critical roles for c-Myb in lymphoid priming and early B-cell development.
c-Myb is a transcription factor with functions in many hematopoietic lineages. c-Myb-deficient mice display reduced numbers of B cells; however, it is unknown what role c-Myb plays in B lymphopoiesis because no critical target genes have been identified in the B-cell lineage. We demonstrate that conditional deletion of c-Myb in B-cell progenitors completely abolishes B-cell development. c-Myb is required for lymphoid progenitors to respond to the cytokines interleukin-7 and thymic stromal lymphopoietin; in the absence of sufficient c-Myb activity, mice display a B lymphopenia that closely resembles that observed in interleukin-7 receptor alpha-deficient animals. Analysis of the multipotent progenitor compartment indicates that c-Myb is also required for up-regulation of multiple lymphoid-associated genes, including Il7r, and for the subsequent development of the common lymphoid progenitor population. These data show that c-Myb plays a critical role in the regulatory pathways governing lymphoid specification and early B-cell differentiation.
Greig
Kylie T
KT
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
de Graaf
Carolyn A
CA
Murphy
James M
JM
Carpinelli
Marina R
MR
Pang
Swee Heng Milon
SH
Frampton
Jon
J
Kile
Benjamin T
BT
Hilton
Douglas J
DJ
Nutt
Stephen L
SL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D008231:Lymphopenia / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D015851:Interleukin-7; D020598:Proto-Oncogene Proteins c-myb; D020395:Receptors, Interleukin-7; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse