Characteristics of early murine B-lymphocyte precursors and their direct sensitivity to negative regulators

Taku Kouro, Kay L Medina, Kenji Oritani, Paul W. Kincade

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Recently, a collection of surface markers was exploited to isolate viable Lin- TdT+ cells from murine bone marrow. These early pro-B cells were enriched for B-lineage lymphocyte precursor activity measured by short-term culture and had little responsiveness to myeloid growth factors. Early precursors can be propagated with remarkably high cloning frequencies in stromal cell-free, serum-free cultures, permitting this analysis of direct regulatory factors. Expression of the interleukin-7 receptor (IL-7Rα) chain marks functional precursors and IL-7 is necessary for progression beyond the CD45RA+ CD19- stage. Efficient survival and differentiation were only observed when stem cell factor and Fit-3 ligand were also present. IL-7-responsive CD19+ precursors are estrogen resistant. However, B-lineage differentiation was selectively abrogated when highly purified Lin- precursors were treated with hormone in the absence of stromal cells. In addition, early stages of B lymphopoiesis were arrested by limitin, a new interferon (IFN)-like cytokine as well as IFN-α, IFN-γ, or transforming growth factor β (TGF-β), but not by epidermal growth factor (EGF). Lin- TdT+ early pro-B cells are shown here to be CD27+ AA4.1+/- Ki-67+ Ly-6C- Ly-6A/Sca-1Lo/-Thy-1-CD43+ CD4+/-CD16/32Lo/-CD44Hi and similar in some respects to the "common lymphoid progenitors" (CLP) identified by others. Although early pro-B cells have lost myeloid differentiation potential, transplantation experiments described here reveal that at least some can generate T lymphocytes. Of particular importance is the demonstration that a pivotal early stage of lymphopoiesis is directly sensitive to negative regulation by hormones and cytokines.

Original languageEnglish (US)
Pages (from-to)2708-2715
Number of pages8
JournalBlood
Volume97
Issue number9
DOIs
StatePublished - May 1 2001
Externally publishedYes

Fingerprint

B-Lymphoid Precursor Cells
Lymphocytes
Interferons
Interleukin-7
Cells
Lymphopoiesis
Stromal Cells
Interleukin-7 Receptors
Hormones
Cytokines
Stem Cell Factor
T-cells
Lymphoid Progenitor Cells
Cloning
Transforming Growth Factors
Cell culture
Epidermal Growth Factor
Intercellular Signaling Peptides and Proteins
Bone
Estrogens

ASJC Scopus subject areas

  • Hematology

Cite this

Characteristics of early murine B-lymphocyte precursors and their direct sensitivity to negative regulators. / Kouro, Taku; Medina, Kay L; Oritani, Kenji; Kincade, Paul W.

In: Blood, Vol. 97, No. 9, 01.05.2001, p. 2708-2715.

Research output: Contribution to journalArticle

Kouro, Taku ; Medina, Kay L ; Oritani, Kenji ; Kincade, Paul W. / Characteristics of early murine B-lymphocyte precursors and their direct sensitivity to negative regulators. In: Blood. 2001 ; Vol. 97, No. 9. pp. 2708-2715.
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