Id1 has a physiological role in regulating early B lymphopoiesis.

Basic helix-loop-helix E proteins play critical roles in B-cell development by stimulating B cell-specific gene expression and immunoglobulin gene rearrangement. The function of E proteins can be effectively suppressed by their naturally occurring inhibitors, Id1 to 4. Ectopic expression of Id1 has been shown to block B-cell development at the early pro-B cell stage. However, whether Id1 plays a physiological role in controlling B lymphopoiesis was not known. Although Id1-deficient mice do not exhibit significant abnormalities in steady-state B lymphopoiesis, we detected more robust B-cell engraftment in transplant recipients of Id1-deficient bone marrow compared to those of wild-type donor cells. In culture, Id1 ablation dramatically enhances B-lineage cell production without any marked effects on myeloid differentiation. Consistently, Id1 expression was found in pro-B but not pre-B cells as measured by enhanced green fluorescent protein (EGFP) fluorescence and by quantitative reverse transcription-PCR. Although loss of Id1 did not alter the number of B-cell colonies generated from whole bone marrow or the proliferation rate of developing B cells, B-cell colonies were detectable at a much earlier time point and the size of the colonies were larger. Therefore, we infer that Id1-deficient progenitors possess higher potential to differentiate to the pre-B cell stage when a proliferative burst occurs. Taken together, we present evidence to suggest that Id1 plays a physiological role in restraining the developmental progression, which may be important for proper B-cell differentiation in the bone marrow.