Visualizing antibody affinity maturation in germinal centers.
Visualizing antibody affinity maturation in germinal centers.
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DOI：
10.1126/science.aad3439
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发表时间：
2016-03-04
期刊：
影响因子：
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通讯作者：
Victora GD
中科院分区：
文献类型：
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作者：
Tas JM;Mesin L;Pasqual G;Targ S;Jacobsen JT;Mano YM;Chen CS;Weill JC;Reynaud CA;Browne EP;Meyer-Hermann M;Victora GD
抗体体细胞突变以在生发中心（GC）中获得高亲和力。在那里，B细胞克隆之间和每个克隆的体细胞突变体之间的竞争驱动整个群体的平均亲和力增加。高亲和力细胞消除竞争者限制克隆多样性的程度尚不清楚。通过结合多光子显微镜和测序，我们发现，数十至数百个不同的B细胞克隆种子每个GC，GC失去克隆多样性在很大程度上不同的速度。此外，有效的亲和力成熟可以在没有PCR选择的情况下发生，确保许多克隆可以在同一GC内平行成熟。我们的研究结果对疫苗的开发具有一定的意义，其中必须引起具有非免疫显性特异性的抗体，如HIV-1和流感的情况。
Antibodies somatically mutate to attain high affinity in germinal centers (GCs). There, competition between B cell clones and among somatic mutants of each clone drives an increase in average affinity across the population. The extent to which higher-affinity cells eliminating competitors restricts clonal diversity is unknown. By combining multiphoton microscopy and sequencing, we show that tens to hundreds of distinct B cell clones seed each GC, and that GCs lose clonal diversity at widely disparate rates. Furthermore, efficient affinity maturation can occur in the absence of homogenizing selection, ensuring that many clones can mature in parallel within the same GC. Our findings have implications for development of vaccines in which antibodies with non-immunodominant specificities must be elicited, as is the case for HIV-1 and influenza.