The scaffolding protein synapse-associated protein 97 is required for enhanced signaling through isotype-switched IgG memory B cell receptors.

Abstract

After their first encounter with a foreign antigen, naïve B cells that have immunoglobulin M (IgM) B cell receptors (BCRs) trigger the primary antibody response and the generation of memory B cells with IgG BCRs. When these memory B cells reencounter the same antigen, the cell surface IgG BCRs stimulate their rapid differentiation into plasma cells that release large amounts of IgG antibodies. We showed that the conserved cytoplasmic tail of the IgG BCR, which contains a putative PDZ (postsynaptic density 95/disc large/zona occludens 1)-binding motif, associated with synapse-associated protein 97 (SAP97), a PDZ domain-containing scaffolding molecule that is involved in controlling receptor density and signal strength at neuronal synapses. SAP97 accumulated and bound to IgG BCRs in the immunological synapses that formed in response to B cell engagement with antigen. Knocking down SAP97 in IgG⁺ B cells or mutating the putative PDZ-binding motif in the BCR tail impaired formation of the immunological synapse, initiation of IgG BCR signaling, and downstream activation of the mitogen-activated protein kinase p38. Thus, heightened B cell memory responses are encoded, in part, by a mechanism that involves SAP97 serving as a scaffolding protein in the IgG BCR immunological synapse.

• Authors: Wanli Liu, Elizabeth Chen, Xing Wang Zhao, Zheng Peng Wan, Yi Ren Gao, Angel Davey, Eric Huang, Lijia Zhang, Jillian Crocetti, Gabriel Sandoval, M Gordon Joyce, Carrie Miceli, Jan Lukszo, L Aravind, Wojciech Swat, Joseph Brzostowski, Susan K Pierce
• Journal: Science signaling (Sci Signal) Vol. 5 Issue 235 Pg. ra54 (Jul 31 2012) ISSN: 1937-9145 [Electronic] United States
• PMID: 22855505 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• DLG1 protein, human
• Discs Large Homolog 1 Protein
• Immunoglobulin G
• Lipid Bilayers
• Membrane Proteins
• Receptors, IgG

Topics

• Adaptor Proteins, Signal Transducing (immunology, metabolism)
• Animals
• B-Lymphocytes (immunology)
• Cell Differentiation (immunology)
• Cell Line
• Discs Large Homolog 1 Protein
• Enzyme-Linked Immunosorbent Assay
• Humans
• Immunoglobulin Class Switching (genetics, immunology)
• Immunoglobulin G (immunology)
• Immunologic Memory (immunology)
• Immunoprecipitation
• Lipid Bilayers (immunology)
• Membrane Proteins (immunology, metabolism)
• Mice
• Microscopy, Fluorescence (methods)
• Plasma Cells (immunology)
• Receptors, IgG (immunology, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (immunology)