Synthetic Anti-br3 Antibodies That Mimic Baff Binding and Target Both Human and Murine B Cells.
From: Department of Protein Engineering, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
Blood
- Publish Date: Nov 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 9
- Pages: 3103-11
- Medium: Print
- Language: English
- Citation (JAMA): Lee Chingwei V, Hymowitz Sarah G, Wallweber Heidi J, et al. Synthetic Anti-br3 Antibodies That Mimic Baff Binding and Target Both Human and Murine B Cells.. Blood Nov 2006;108:3103-11
Abstract
BR3, which is 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 tumor necrosis factor [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 extracellular domains. We found an antibody, CB1, which exhibits muM 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.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Antibodies, B-Cell Activating Factor, B-Cell Activation Factor Receptor, B-Lymphocytes, Binding Sites, Crystallography, X-Ray, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin Fab Fragments, Immunoglobulin G, Lymphocyte Activation, Mice, Models, Molecular, Molecular Sequence Data, Mutagenesis, Protein Conformation, Sequence Alignment, Sequence Homology, Amino Acid
Check for Full Text / PubMed Unique Identifier (PMID): 16840730
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.