MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS, UK.
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
Curr Opin Immunol. 2017 Apr;45:21-30. doi: 10.1016/j.coi.2016.12.004. Epub 2017 Jan 12.
The seminal discovery by Eisen that antibodies undergo improvements in antigen-binding affinity over the course of an immune response led to a long running search for the underlying mechanism. Germinal centers in lymphoid organs are now recognized to be critically involved in this phenomenon, known as antibody affinity maturation. As well as improving in affinity for specific epitopes, some antibody responses maintain or even increase their breadth of antigen-recognition over time. This has led to another intense line of research aimed at understanding how broadly neutralizing anti-pathogen responses are generated. Recent work indicates that germinal centers also play an important role in the diversification process. We discuss current understanding of how germinal centers are programmed to support both affinity maturation and antibody diversification.
伊森（Eisen）的开创性发现表明，抗体在免疫反应过程中会提高抗原结合亲和力，这促使人们长期寻找其潜在机制。现在人们已经认识到，淋巴器官中的生发中心在这一被称为抗体亲和力成熟的现象中起着至关重要的作用。除了提高对特定表位的亲和力外，一些抗体反应随着时间的推移还能保持甚至增加其抗原识别的广度。这导致了另一项旨在了解如何产生广泛中和抗病原体反应的激烈研究。最近的工作表明，生发中心在多样化过程中也起着重要作用。我们讨论了当前对生发中心如何编程以支持亲和力成熟和抗体多样化的理解。
