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The microprocessor component, DGCR8, is essential for early B-cell development in mice.

Andreas Brandl1, Patrick Daum1, Sven Brenner2

  • 1Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany.

European Journal of Immunology
|September 20, 2016
PubMed
Summary

The microprocessor component DiGeorge Critical Region 8 (DGCR8) is essential for B-cell development. Deleting DGCR8 in mice blocks pro-B to pre-B cell maturation and impairs survival of early B-cell progenitors.

Keywords:
B cells · DGCR8 · Drosha · microRNA · pre-BCR

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) regulate gene expression post-transcriptionally.
  • The microprocessor complex, comprising Drosha and DiGeorge Critical Region 8 (DGCR8), processes primary miRNAs.
  • DGCR8 is crucial for lymphocyte development.

Purpose of the Study:

  • To investigate the role of DGCR8 in B-cell development.
  • To determine the impact of DGCR8 deletion on B-cell maturation and survival.

Main Methods:

  • Utilized cre-mediated B-cell specific deletion of DGCR8 in mice.
  • Analyzed B-cell maturation stages (pro-B to pre-B).
  • Assessed Ig μ heavy chain expression and cell viability.

Main Results:

  • B-cell specific DGCR8 deletion caused a maturation block at the pro-B to pre-B transition.
  • Failed to upregulate Ig μ heavy chain expression in pro-B cells.
  • Enforced Bcl2 expression partially rescued DGCR8-deficient pro-B cell death.

Conclusions:

  • DGCR8 is essential for the survival of early B-cell progenitors.
  • DGCR8 plays a critical role in B-cell differentiation.
  • The microprocessor complex is vital for hematopoietic lineage commitment.