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Unité du Développement des Lymphocytes, Institute National de la Santé et de la Recherche Medicale U668, Institut Pasteur, 75724 Paris, France

CORRESPONDENCE Ana Cumano: cumano{at}pasteur.fr

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.

Abbreviations used: c, common -chain; CLP, common lymphoid progenitor; EBF, early B cell factor; ELP, early lymphocyte precursor; FTOC, fetal thymic organ culture; HSC, hematopoietic stem cell; Lin^–, lineage^–; TSLP, thymic-stromal lymphopoietin.

H. Silva Jr.'s present address is Laboratório de Proliferação e Diferenciação Celular, Instituto de Ciencias Biomédicas-UFRJ, Centro de Ciencias da Saúde, CEP 21941-970, Brasil.

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