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Id1 has a physiological role in regulating early B lymphopoiesis

Cellular & Molecular Immunology volume 8, pages 41–49 (2011)Cite this article

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.

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Acknowledgements

We thank Dr Carol Webb for critical reading of the manuscript and Dr Hong-Cheng Wang for assistance in data analyses. We are grateful to the flow cytometry facility at the Oklahoma Medical Research Foundation for technical support. This work was supported by the grant to XHS (NIH AI56129). XHS holds the Lew and Myra Ward Chair in Biomedical Research.

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Authors and Affiliations

  1. Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    Shawn W Cochrane, Ying Zhao, SScott Perry, Thomas Urbaniak & Xiao-Hong Sun

  2. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Shawn W Cochrane & Xiao-Hong Sun

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Correspondence to Xiao-Hong Sun.

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Cochrane, S., Zhao, Y., Perry, S. et al. Id1 has a physiological role in regulating early B lymphopoiesis. Cell Mol Immunol 8, 41–49 (2011). https://doi.org/10.1038/cmi.2010.58

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