Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation.
Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation.
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DOI：
10.1016/j.immuni.2015.06.013
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发表时间：
2015-07-21
期刊：
影响因子：
32.4
通讯作者：
Shlomchik MJ
中科院分区：
文献类型：
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作者：
Di Niro R;Lee SJ;Vander Heiden JA;Elsner RA;Trivedi N;Bannock JM;Gupta NT;Kleinstein SH;Vigneault F;Gilbert TJ;Meffre E;McSorley SJ;Shlomchik MJ
B细胞对鼠伤寒沙门氏菌(STM)的反应主要发生在卵泡外部位，没有明显的生发中心(GC)。人们对其特异性知之甚少。为了扩大对抗原靶标的了解，我们使用ELISA、流式细胞术和抗原芯片筛选了来自浆母细胞(PB)的沙门氏菌特异性单抗。只有一小部分(0.5%-2%)的反应似乎是沙门氏菌特异性的。然而，感染具有有限B细胞受体(BCR)谱系的小鼠会损害这种反应，这表明BCR的特异性是重要的。我们使用激光显微解剖技术显示，体细胞超突变(SHM)有效地发生在卵泡外部位，导致亲和力成熟，进而导致可检测到的STM抗原结合。这些结果表明，对克隆选择和亲和力成熟是如何对沙门氏菌做出反应的看法进行了修订。克隆选择最初是混杂的，以几乎无法检测到的亲和力激活细胞，但SHM和选择发生在卵泡外反应期间，产生更高亲和力的可检测抗体。
The B cell response to Salmonella typhimurium (STm) occurs massively at extrafollicular sites, without notable germinal centers (GCs). Little is known in terms of its specificity. To expand the knowledge of antigen targets, we screened plasmablast (PB)-derived monoclonal antibodies (mAbs) for Salmonella specificity, using ELISA, flow cytometry, and antigen microarray. Only a small fraction (0.5%–2%) of the response appeared to be Salmonella-specific. Yet, infection of mice with limited B cell receptor (BCR) repertoires impaired the response, suggesting that BCR specificity was important. We showed, using laser microdissection, that somatic hypermutation (SHM) occurred efficiently at extrafollicular sites leading to affinity maturation that in turn led to detectable STm Ag-binding. These results suggest a revised vision of how clonal selection and affinity maturation operate in response to Salmonella. Clonal selection initially is promiscuous, activating cells with virtually undetectable affinity, yet SHM and selection occur during the extrafollicular response yielding higher affinity, detectable antibodies.