The germinal center antibody response in health and disease.
The germinal center antibody response in health and disease.
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DOI：
10.12688/f1000research.7717.1
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
DeFranco, Anthony L
中科院分区：
文献类型：
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作者：
DeFranco, Anthony L
生发中心反应是抗体反应的延迟但持续的阶段，其负责产生IgG、伊加和/或IgE同种型的高亲和力抗体。生发中心的B细胞经历免疫球蛋白基因可变区的体细胞超突变、克隆扩增和表达更高亲和力抗体变体的细胞的达尔文选择的再迭代循环。或者，选择的B细胞可以终末分化为长寿的浆细胞或多种多样的突变记忆B细胞;前者分泌改进的抗体以对抗感染并提供持续的保护以防止再次感染，而后者可以快速启动对相关但不同的感染因子的后续感染的免疫应答。我们对参与生发中心反应的分子的理解是通过对抗体产生有选择性缺陷的人类免疫缺陷患者的研究得到的。最近的研究已经开始揭示通过Toll样受体的先天免疫识别如何增强生发中心的大小和选择性，从而更有效地控制病毒子集的感染。正如早期对生发中心性质的认识在非常成功的结合疫苗的开发中得到应用一样，最近的认识可能会在目前开发新一代疫苗的努力中得到应用，包括可以诱导针对流感病毒或HIV-1的广泛保护性中和抗体的疫苗。
The germinal center response is the delayed but sustained phase of the antibody response that is responsible for producing high-affinity antibodies of the IgG, IgA and/or IgE isotypes. B cells in the germinal center undergo re-iterative cycles of somatic hypermutation of immunoglobulin gene variable regions, clonal expansion, and Darwinian selection for cells expressing higher-affinity antibody variants. Alternatively, selected B cells can terminally differentiate into long-lived plasma cells or into a broad diversity of mutated memory B cells; the former secrete the improved antibodies to fight an infection and to provide continuing protection from re-infection, whereas the latter may jumpstart immune responses to subsequent infections with related but distinct infecting agents. Our understanding of the molecules involved in the germinal center reaction has been informed by studies of human immunodeficiency patients with selective defects in the production of antibodies. Recent studies have begun to reveal how innate immune recognition via Toll-like receptors can enhance the magnitude and selective properties of the germinal center, leading to more effective control of infection by a subset of viruses. Just as early insights into the nature of the germinal center found application in the development of the highly successful conjugate vaccines, more recent insights may find application in the current efforts to develop new generations of vaccines, including vaccines that can induce broadly protective neutralizing antibodies against influenza virus or HIV-1.