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 suppress...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.展开更多
基金This work was supported by the grant to XHS(NIH AI56129).
文摘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.
