IL-7 specifies B cell fate at the common lymphoid progenitor to pre-proB transition stage by maintaining early B cell factor expression.
IL-7 plays a critical role in B cell fate decision by regulating early B cell factor (EBF) expression. However, it was not clear when IL-7 stimulation is necessary in hemato-/lymphopoiesis in adult mice. Here we show that pre-proB cells derived from IL-7-/- mice have lost B cell potential, despite up-regulation of EBF expression following IL-7 stimulation. Pre-proB cells from wild-type mice can give rise to proB cells in the absence of IL-7. In this case, EBF up-regulation during the transition from the pre-proB to proB stages occurs normally. In contrast, EBF expression by IL-7-/- pre-proB cells after IL-7 stimulation is approximately 20 times lower than wild-type pre-proB cells. In addition, only multipotent progenitors with higher levels of ectopic EBF can give rise to proB cells in the absence of IL-7. Therefore, the primary function of IL-7 before the pre-proB stage in B cell development is to maintain the EBF expression level above a certain threshold, which is necessary for pre-proB cells to further transit to the proB stage.
Kikuchi
Kazu
K
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Kasai
Hirotake
H
Watanabe
Akiko
A
Lai
Anne Y
AY
Kondo
Motonari
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
C489921:Ebf1 protein, mouse; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D015534:Trans-Activators