Bifunctional CD22 Ligands Use Multimeric Immunoglobulins as Protein Scaffolds in Assembly of Immune Complexes on B Cells

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• 作者：Mary K. O’ ; Reilly ; Brian E. Collins ; Shoufa Han ; Liang Liao ; Cory Rillahan ; Pavel I. Kitov ; David R. Bundle ; James C. Paulson
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：June 18, 2008
• 年：2008
• 卷：130
• 期：24
• 页码：7736 - 7745
• 全文大小：1303K
• 年卷期：v.130,no.24(June 18, 2008)
• ISSN：1520-5126

文摘

CD22 is a B cell-specific sialic acid-binding immunoglobulin-like lectin (Siglec) whose function as a regulator of B cell signaling is modulated by its interaction with glycan ligands bearing the sequence NeuAcα2−6Gal. To date, only highly multivalent polymeric ligands (n = 450) have achieved sufficient avidity to bind to CD22 on native B cells. Here we demonstrate that a synthetic bifunctional molecule comprising a ligand of CD22 linked to an antigen (nitrophenol; NP) can use a monoclonal anti-NP IgM as a decavalent protein scaffold to efficiently drive assembly of IgM−CD22 complexes on the surface of native B cells. Surprisingly, anti-NP antibodies of lower valency, IgA (n = 4) and IgG (n = 2), were also found to drive complex formation, though with lower avidity. Ligands bearing alternate linkers of variable length and structure were constructed to establish the importance of a minimal length requirement, and versatility in the structural requirement. We show that the ligand drives assembly of IgM complexes exclusively on the surface of B cells and not other classes of white blood cells that do not express CD22, which lends itself to the possibility of targeting B cells in certain hematopoietic malignancies.