在第一次遇到外来抗原后，具有免疫球蛋白M（IgM）B细胞受体（BCRs）的初始B细胞引发首次抗体反应，并产生具有IgG BCRs的记忆B细胞。当这些记忆B细胞再次遇到相同的抗原时，细胞表面的IgG BCRs刺激它们迅速分化成浆细胞释放大量的IgG抗体。
7月31日，SCI SIGNAL杂志报道免疫系统通过IgG BCRs介导信号通路，确保记忆B细胞对再次遇见的病原体快速而高效地作出反应的机制。
研究表明，IgG BCRs保守的胞质区尾部包含一个假定的PDZ（postsynaptic density 95/disc large/zona occludens 1）结合基序。该尾部区域与突触相关蛋白97（SAP97）相关。SAP97 是一种包含PDZ结构域的脚手架分子，参与控制神经突触受体密度和信号强度。
在B细胞处理抗原过程中形成了免疫突触。在这些免疫突触中，SAP97积累并结合到IgG BCRs上。在IgG+ B细胞中下调SAP97或突变BCR尾部的PDZ-结合基序，可阻碍免疫突触的形成，IgG BCR信号的起始，以及有丝分裂原活化蛋白激酶p38的下游激活。
总之，在IgG BCR免疫突触中，脚手架蛋白SAP97增强了B细胞记忆反应。B细胞记忆反应调节机制的进一步揭示，对于诱导免疫系统高效抗击病原体入侵具有重要意义。SAP97或可成为免疫治疗的新靶点。（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.
