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Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen

Nature Immunology volume 2, pages 718–724 (2001)Cite this article

Abstract

Estrogen is a negative regulator of lymphopoiesis and provides an experimental tool for probing relationships between lymphocyte precursors and stem cells. We found that expression of lymphocyte-associated genes and immunoglobulin (Ig) gene rearrangement occurred before CD45R acquisition. Lymphoid-restricted progenitors that were Lin−IL-7Rα+c-kitloTdT+ (lineage marker−, interleukin receptor 7α+, c-kitlo and terminal deoxynucleotidyl transferase+) were selectively depleted in estrogen-treated mice; within a less differentiated Lin−c-kithi fraction, functional precursors of B and T, but not myeloid, cells were also selectively depleted. TdT and an Ig heavy chain transgene were detected within a hormone-regulated Lin−c-kithiSca-1+CD27+Flk-2+IL-7Rα− subset of this multipotential progenitor population. Identification of these extremely early lymphoid precursors should facilitate investigation of the molecular mechanisms that control lineage-fate decisions in hematopoiesis.

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Figure 1: Early B lineage differentiation events are initiated before CD45R acquisition.
Figure 2: Estrogen treatment reduced the frequency and mitotic activity of early lymphoid progenitor cells.
Figure 3: Multipotential precursors that were capable of generating B lineage cells were reduced in hormone-treated mice.
Figure 4: Multipotential precursors capable of generating T lineage cells were reduced in hormone-treated mice.
Figure 5: Expression of a μ transgene and TdT initiated within the multipotential progenitor compartment of bone marrow and was ablated in hormone-treated animals.
Figure 6: Coexpression of TdT and a μ chain transgene within an early, hormone-sensitive, Lin− compartment.

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Acknowledgements

We thank L. Borghesi for critical review of the manuscript and V. Dandapani for flow cytometry and sorting expertise. Supported by the National Institutes of Health (AI 20069).

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  1. Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, 73104, OK, USA

    Kay L. Medina, Karla P. Garrett, Linda F. Thompson, Maria Isabel D. Rossi, Kimberly J. Payne & Paul W. Kincade

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Correspondence to Paul W. Kincade.

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Medina, K., Garrett, K., Thompson, L. et al. Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen. Nat Immunol 2, 718–724 (2001). https://doi.org/10.1038/90659

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