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Molecular and Cellular Biology, February 2004, p. 997-1006, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.997-1006.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

APRIL-Deficient Mice Have Normal Immune System Development

Eugene Varfolomeev,1 Frank Kischkel,1 Flavius Martin,2 Dhaya Seshasayee,2 Hua Wang,2 David Lawrence,1 Christine Olsson,3 Lucrece Tom,3 Sharon Erickson,3 Dorothy French,4 Peter Schow,2 Iqbal S. Grewal,2 and Avi Ashkenazi1*

Departments of Molecular Oncology,1 Immunology,2 Physiology,3 Pathology, Genentech Inc., South San Francisco, California4

Received 27 August 2003/ Returned for modification 9 October 2003/ Accepted 30 October 2003

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.

* Corresponding author. Mailing address: Department of Molecular Oncology, Genentech Inc., South San Francisco, CA 94080. Phone: (650) 225-1853. Fax: (650) 225-1853. E-mail: aa{at}gene.com. {dagger} E.V. and F.K. contributed equally to this work.

Molecular and Cellular Biology, February 2004, p. 997-1006, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.997-1006.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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