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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3103-3111. Prepublished online as a Blood First Edition Paper on July 13, 2006; DOI 10.1182/blood-2006-03-011031. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-03-011031v1 108/9/3103    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, C. V Articles by Fuh, G. Search for Related Content PubMed PubMed Citation Articles by Lee, C. V Articles by Fuh, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 21, 2006 Accepted June 21, 2006 Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells Chingwei V Lee, Sarah G Hymowitz, Heidi J Wallweber, Nathaniel C Gordon, Karen L Billeci, Siao-Ping Tsai, Deanne M Compaan, Jian Ping Yin, Qian Gong, Robert F Kelley, Laura E DeForge, Flavius Martin, Melissa A Starovasnik, and Germaine Fuh* Department of Protein Engineering, Genentech Inc., San Francisco, CA, USA Assay and Automation Technology, Genentech Inc., San Francisco, CA, USA Department of Immunology, Genentech Inc., San Francisco, CA, USA Department of Protein Engineering and Immunology, Genentech Inc., San Francisco, CA, USA * Corresponding author; email: gml{at}gene.com. BR3, expressed on all mature B cells, is a specific receptor for the B cell survival and maturation factor BAFF (B cell-activating factor belonging to the TNF family). In order to investigate the consequences of targeting BR3 in murine models and to assess the potential of BR3 antibodies as human therapeutics, synthetic antibody phage libraries were employed to identify BAFF-blocking antibodies cross-reactive to murine and human BR3, which share 52% identity in their extra-cellular domains. An antibody, CB1, was found, which exhibits ?M affinity for murine BR3, and very weak affinity for the human receptor. CB3s, an affinity-matured variant of CB1, has sub-nM affinity for BR3 from both species. Alanine scanning and crystallographic structural analysis of the CB3s/BR3 complex reveal that CB3s mimics BAFF by interacting with a similar region of the BR3 surface. Despite this similarity in binding epitopes, CB1 variants antagonize BAFF-dependent human B cell proliferation in vitro and are effective at reducing murine B cell populations in vivo, showing significant promise as therapeutics for human B-cell-mediated diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Synthetic antibodies prey on B cells Christoph Rader and Carlos F. Barbas, III Blood 2006 108: 2889-2890. [Full Text] [PDF]

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