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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.

SUBMITTER: Liu W 

PROVIDER: S-EPMC3413325 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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

Liu Wanli W   Chen Elizabeth E   Zhao Xing Wang XW   Wan Zheng Peng ZP   Gao Yi Ren YR   Davey Angel A   Huang Eric E   Zhang Lijia L   Crocetti Jillian J   Sandoval Gabriel G   Joyce M Gordon MG   Miceli Carrie C   Lukszo Jan J   Aravind L L   Swat Wojciech W   Brzostowski Joseph J   Pierce Susan K SK  

Science signaling 20120731 235


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 (postsynapt  ...[more]

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