This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Varfolomeev, E.
Right arrow Articles by Ashkenazi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varfolomeev, E.
Right arrow Articles by Ashkenazi, A.

 Previous Article  |  Next Article 

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.



This article has been cited by other articles:

  • Kimberley, F. C., van Bostelen, L., Cameron, K., Hardenberg, G., Marquart, J. A., Hahne, M., Medema, J. P. (2009). The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization and cross-linking. FASEB J. 23: 1584-1595 [Abstract] [Full Text]  
  • Carbonatto, M., Yu, P., Bertolino, M., Vigna, E., Steidler, S., Fava, L., Daghero, C., Roattino, B., Onidi, M., Ardizzone, M., Peano, S., Visich, J., Janszen, D., Dillon, S., Ponce, R. (2008). Nonclinical Safety, Pharmacokinetics, and Pharmacodynamics of Atacicept. Toxicol Sci 105: 200-210 [Abstract] [Full Text]  
  • Hardenberg, G., Fernandez, L., Hendriks, J., Chebli, K., Jacquet, C., Sitbon, M., Hahne, M., Medema, J. P. (2008). APRIL facilitates viral-induced erythroleukemia but is dispensable for T cell immunity and lymphomagenesis. J. Leukoc. Biol. 84: 380-388 [Abstract] [Full Text]  
  • Belnoue, E., Pihlgren, M., McGaha, T. L., Tougne, C., Rochat, A.-F., Bossen, C., Schneider, P., Huard, B., Lambert, P.-H., Siegrist, C.-A. (2008). APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood 111: 2755-2764 [Abstract] [Full Text]  
  • Bossen, C., Cachero, T. G., Tardivel, A., Ingold, K., Willen, L., Dobles, M., Scott, M. L., Maquelin, A., Belnoue, E., Siegrist, C.-A., Chevrier, S., Acha-Orbea, H., Leung, H., Mackay, F., Tschopp, J., Schneider, P. (2008). TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts. Blood 111: 1004-1012 [Abstract] [Full Text]  
  • Woodland, R. T., Fox, C. J., Schmidt, M. R., Hammerman, P. S., Opferman, J. T., Korsmeyer, S. J., Hilbert, D. M., Thompson, C. B. (2008). Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood 111: 750-760 [Abstract] [Full Text]  
  • Chu, V. T., Enghard, P., Riemekasten, G., Berek, C. (2007). In Vitro and In Vivo Activation Induces BAFF and APRIL Expression in B Cells. J. Immunol. 179: 5947-5957 [Abstract] [Full Text]  
  • Mantchev, G. T., Cortesao, C. S., Rebrovich, M., Cascalho, M., Bram, R. J. (2007). TACI Is Required for Efficient Plasma Cell Differentiation in Response to T-Independent Type 2 Antigens. J. Immunol. 179: 2282-2288 [Abstract] [Full Text]  
  • Schwaller, J., Schneider, P., Mhawech-Fauceglia, P., McKee, T., Myit, S., Matthes, T., Tschopp, J., Donze, O., Le Gal, F.-A., Huard, B. (2007). Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness. Blood 109: 331-338 [Abstract] [Full Text]  
  • Huntington, N. D., Tomioka, R., Clavarino, C., Chow, A. M., Linares, D., Mana, P., Rossjohn, J., Cachero, T. G., Qian, F., Kalled, S. L., Bernard, C. C. A., Reid, H. H. (2006). A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses. Int Immunol 18: 1473-1485 [Abstract] [Full Text]  
  • Zheng, Y., Gallucci, S., Gaughan, J. P., Gross, J. A., Monestier, M. (2005). A Role for B Cell-Activating Factor of the TNF Family in Chemically Induced Autoimmunity. J. Immunol. 175: 6163-6168 [Abstract] [Full Text]  
  • Yang, M., Hase, H., Legarda-Addison, D., Varughese, L., Seed, B., Ting, A. T. (2005). B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells. J. Immunol. 175: 2814-2824 [Abstract] [Full Text]  
  • Nishio, M., Endo, T., Tsukada, N., Ohata, J., Kitada, S., Reed, J. C., Zvaifler, N. J., Kipps, T. J. (2005). Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1{alpha}. Blood 106: 1012-1020 [Abstract] [Full Text]  
  • Merrill, J T (2005). BLyS antagonists and peptide tolerance induction. Lupus 14: 204-209 [Abstract]  
  • Sasaki, Y., Casola, S., Kutok, J. L., Rajewsky, K., Schmidt-Supprian, M. (2004). TNF Family Member B Cell-Activating Factor (BAFF) Receptor-Dependent and -Independent Roles for BAFF in B Cell Physiology. J. Immunol. 173: 2245-2252 [Abstract] [Full Text]  
  • Patel, D. R., Wallweber, H. J. A., Yin, J., Shriver, S. K., Marsters, S. A., Gordon, N. C., Starovasnik, M. A., Kelley, R. F. (2004). Engineering an APRIL-specific B Cell Maturation Antigen. J. Biol. Chem. 279: 16727-16735 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»