title: Id1 has a physiological role in regulating early B lymphopoiesis.
abstract: 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.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Shawn W
authors.initials: SW
authors.lastname: Cochrane
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: S Scott
authors.initials: SS
authors.lastname: Perry
authors.forename: Thomas
authors.initials: T
authors.lastname: Urbaniak
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Sun
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000276:immunology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006085:Graft Survival / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D051798:Inhibitor of Differentiation Protein 1