Wardemann Hedda, Yurasov Sergey, Schaefer Anne, Young James W, Meffre Eric, Nussenzweig Michel C
Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA.
Science. 2003 Sep 5;301(5638):1374-7. doi: 10.1126/science.1086907. Epub 2003 Aug 14.
During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.
在B淋巴细胞发育过程中，抗体通过随机基因片段重排组装而成，从而产生大量具有特异性的抗体。这一过程的一个潜在缺点是所产生的一些抗体具有自身反应性。我们确定了人类B细胞中自身反应性抗体形成的发生率及其调控机制。早期未成熟B细胞表达的所有抗体中，大部分（55%至75%）表现出自身反应性，包括多反应性和抗核特异性。在B细胞发育过程中的两个离散检查点，这些自身抗体中的大多数从细胞群体中被清除。检查点调控效率低下会导致循环自身抗体大幅增加。
