IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF.
Cytokine receptor signals have been suggested to stimulate cell differentiation during hemato/lymphopoiesis. Such action, however, has not been clearly demonstrated. Here, we show that adult B cell development in IL-7(-/-) and IL-7R alpha(2/-) mice is arrested at the pre-pro-B cell stage due to insufficient expression of the B cell-specific transcription factor EBF and its target genes, which form a transcription factor network in determining B lineage specification. EBF expression is restored in IL-7(-/-) pre-pro-B cells upon IL-7 stimulation or in IL-7R alpha(-/-) pre-pro-B cells by activation of STAT5, a major signaling molecule downstream of the IL-7R signaling pathway. Furthermore, enforced EBF expression partially rescues B cell development in IL-7R alpha(-/-) mice. Thus, IL-7 receptor signaling is a participant in the formation of the transcription factor network during B lymphopoiesis by up-regulating EBF, allowing stage transition from the pre-pro-B to further maturational stages.
Kikuchi
Kazu
K
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Lai
Anne Y
AY
Hsu
Chia-Lin
CL
Kondo
Motonari
M
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008894:Milk Proteins / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D015851:Interleukin-7; D008894:Milk Proteins; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; D015534:Trans-Activators