Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors.
Interleukin-7 (IL-7) promotes survival and expansion of lymphoid precursors. We show here that, in addition, IL-7 has a fundamental role, as early as the stage of the multipotent (B/T/NK) common lymphoid progenitor (CLP), in maintaining the B cell differentiation program open. CLPs generated in the absence of IL-7 have normal T/NK differentiation potential, but severely impaired B potential. Accordingly, CLPs from IL-7-deficient mice express lower amounts of early B cell factor (EBF) and Pax5 than wild-type CLPs, but similar amounts of GATA-3. Importantly, induced overexpression of EBF is sufficient to restore the B potential in these cells. These results indicate that IL-7 directs commitment of CLPs by modulating EBF expression. This is the first example of a cytokine influencing lymphoid lineage commitment in multipotent progenitors and highlights the relevance of the expression of a functional IL-7 receptor at the CLP stage.
Dias
Sheila
S
Unité du Développement des Lymphocytes, Institute National de la Santé et de la Recherche Medicale U668, Institut Pasteur, 75724 Paris, France.
Silva
Hamilton
H
Cumano
Ana
A
Vieira
Paulo
P
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D015851:Interleukin-7 / Q000172:deficiency / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000502:physiology*; D051757:PAX5 Transcription Factor; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015851:Interleukin-7; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D020395:Receptors, Interleukin-7; D015534:Trans-Activators; D014157:Transcription Factors