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APRIL-deficient mice have normal immune system development.

Eugene Varfolomeev1, Frank Kischkel, Flavius Martin

  • 1Department of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA.

Molecular and Cellular Biology
|January 20, 2004
PubMed
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The study found that a proliferation-inducing ligand (APRIL) is not essential for mouse development or immune function. APRIL-deficient mice showed normal B-cell and T-cell activity, suggesting BLyS/BAFF may compensate for APRIL’s role.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • APRIL (a proliferation-inducing ligand) is a TNF superfamily member with high expression in tumors.
  • APRIL interacts with TNF receptors TACI and BCMA, similar to BLyS/BAFF.
  • BLyS/BAFF regulates B-cell function and binds to BAFF-R, a receptor not shared by APRIL.

Purpose of the Study:

  • To investigate the physiological role of APRIL in vivo.
  • To determine if APRIL is essential for normal mouse development and immune function.

Main Methods:

  • Generation of APRIL-deficient (APRIL-/-) mice.
  • Histological analysis of major tissues and immune organs.
  • Assessment of T-cell and B-cell development and function in vitro and in vivo.

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Main Results:

  • APRIL-/- mice were viable, fertile, and showed no gross abnormalities.
  • No defects were observed in major organs or primary/secondary immune organs.
  • T-cell and B-cell development, in vitro function, and in vivo humoral responses were normal.

Conclusions:

  • APRIL is dispensable for proper mouse development and immune homeostasis.
  • BLyS/BAFF may be capable of fulfilling the primary functions of APRIL in mice.