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PMID: 14729948 Published · ppublish English Journal Article

APRIL-deficient mice have normal immune system development.

Molecular and cellular biology ·Vol. 24 ·No. 3 ·2004-02-00 ·Pages 997-1006

Varfolomeev E, Kischkel F, Martin F, Seshasayee D, Wang H, Lawrence D, Olsson C, Tom L, Erickson S, French D, Schow P, Grewal IS, Ashkenazi A

Abstract

APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL(-/-) mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions.

MeSH Terms
Animals B-Lymphocytes/physiology Immune System/physiology Membrane Proteins/deficiency,genetics,physiology Mice Mice, Knockout Phenotype Sequence Deletion T-Lymphocytes/physiology Tumor Necrosis Factor Ligand Superfamily Member 13 Tumor Necrosis Factor-alpha/deficiency,genetics,physiology
Chemicals
Membrane Proteins Tnfsf13 protein, mouse Tumor Necrosis Factor Ligand Superfamily Member 13 Tumor Necrosis Factor-alpha
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Varfolomeev Eugene
Department of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA.
Kischkel Frank
Martin Flavius
Seshasayee Dhaya
Wang Hua
Lawrence David
Olsson Christine
Tom Lucrece
Erickson Sharon
French Dorothy
Schow Peter
Grewal Iqbal S
Ashkenazi Avi
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.3.997-1006.2004
Published
2004-02-00
Pages
997-1006
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC321448
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.3.997-1006.2004 PMC Full Text View journal details
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