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Isolation of Precursor B-cell Subsets from Umbilical Cord Blood
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Published on: April 16, 2013

The earliest step in B lineage differentiation from common lymphoid progenitors is critically dependent upon

Juli P Miller1, David Izon, William DeMuth

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

The Journal of Experimental Medicine
|September 5, 2002
PubMed

Insights

Interleukin-7 (IL-7) is essential for early B cell development. This study shows IL-7 signaling is required for differentiating common lymphoid progenitors (CLPs) into B lineage cells in vivo.

Area of Science:

  • Immunology
  • Developmental Biology
  • Hematopoiesis

Background:

  • Early B cell development from common lymphoid progenitors (CLPs) is not fully understood.
  • Interleukin-7 (IL-7) is a cytokine implicated in lymphocyte development.

Purpose of the Study:

  • To investigate the role of IL-7 in the earliest stages of B cell differentiation.
  • To determine if IL-7 receptor (IL-7R) signaling is essential for in vivo B lineage development.

Main Methods:

  • Utilized a stromal-free culture system to assess IL-7's effect on CLP differentiation.
  • Analyzed B cell precursor frequencies in adult mice lacking IL-7R alpha or gamma(c) chains.

Main Results:

  • IL-7 alone induced differentiation of CLPs into B220(+) CD19(+) B lineage progenitors in vitro.
  • Mice lacking IL-7R alpha or gamma(c) chains showed a complete absence of downstream early B lineage precursors, including pre-pro-B cells.
  • CLP frequencies were normal in gamma(c)(-/-) mice, indicating a defect post-CLP stage.

Conclusions:

  • IL-7 signaling is sufficient for in vitro B lineage commitment from CLPs.
  • IL-7R signaling is critical and requisite for the earliest phases of B cell development in vivo, challenging prior assumptions.
  • Loss of IL-7R signaling impacts B cell development at a more primitive stage than previously thought.

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