在第一次遇到外來(lái)抗原后,，具有免疫球蛋白M（IgM）B細(xì)胞受體（BCRs）的初始B細(xì)胞引發(fā)首次抗體反應(yīng)，并產(chǎn)生具有IgG BCRs的記憶B細(xì)胞,。當(dāng)這些記憶B細(xì)胞再次遇到相同的抗原時(shí)，細(xì)胞表面的IgG BCRs刺激它們迅速分化成漿細(xì)胞釋放大量的IgG抗體,。
7月31日,，SCI SIGNAL雜志報(bào)道免疫系統(tǒng)通過(guò)IgG BCRs介導(dǎo)信號(hào)通路，確保記憶B細(xì)胞對(duì)再次遇見的病原體快速而高效地作出反應(yīng)的機(jī)制,。
研究表明,，IgG BCRs保守的胞質(zhì)區(qū)尾部包含一個(gè)假定的PDZ（postsynaptic density 95/disc large/zona occludens 1）結(jié)合基序,。該尾部區(qū)域與突觸相關(guān)蛋白97（SAP97）相關(guān)。SAP97 是一種包含PDZ結(jié)構(gòu)域的腳手架分子,，參與控制神經(jīng)突觸受體密度和信號(hào)強(qiáng)度,。
在B細(xì)胞處理抗原過(guò)程中形成了免疫突觸。在這些免疫突觸中,，SAP97積累并結(jié)合到IgG BCRs上,。在IgG+ B細(xì)胞中下調(diào)SAP97或突變BCR尾部的PDZ-結(jié)合基序，可阻礙免疫突觸的形成,，IgG BCR信號(hào)的起始,，以及有絲分裂原活化蛋白激酶p38的下游激活。
總之,，在IgG BCR免疫突觸中,，腳手架蛋白SAP97增強(qiáng)了B細(xì)胞記憶反應(yīng)。B細(xì)胞記憶反應(yīng)調(diào)節(jié)機(jī)制的進(jìn)一步揭示,，對(duì)于誘導(dǎo)免疫系統(tǒng)高效抗擊病原體入侵具有重要意義,。SAP97或可成為免疫治療的新靶點(diǎn)。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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The Scaffolding Protein Synapse-Associated Protein 97 Is Required for Enhanced Signaling Through Isotype-Switched IgG Memory B Cell Receptors
Wanli Liu1,2, Elizabeth Chen1*, Xing Wang Zhao2*, Zheng Peng Wan2*, Yi Ren Gao2*, Angel Davey1*, Eric Huang1, Lijia Zhang1, Jillian Crocetti3,4, Gabriel Sandoval5, M. Gordon Joyce1, Carrie Miceli3,4, Jan Lukszo6, L. Aravind7, Wojciech Swat5, Joseph Brzostowski1, and Susan K. Pierce1
After their first encounter with a foreign antigen, na?ve 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.
