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B lymphocyte development is regulated by the nuclear proteins Early B cell factor (EBF) and Pax-5. EBF and Pax-5 work separately and in concert to activate genes required for B cell differentiation. Recent studies have defined mechanisms by which these two factors control transcription, including chromatin remodeling activities and recruitment of partner proteins. This review addresses the structures, functions, and roles of these proteins in early B cell commitment and development, as well as in later stages of B cell differentiation.

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 ∼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.