Visualizing antibody affinity maturation in germinal centers

被引:308
作者
Tas, Jeroen M. J. [1 ]
Mesin, Luka [1 ]
Pasqual, Giulia [1 ]
Targ, Sasha [1 ]
Jacobsen, Johanne T. [1 ]
Mano, Yasuko M. [1 ]
Chen, Casie S. [1 ]
Weill, Jean-Claude [2 ]
Reynaud, Claude-Agnes [2 ]
Browne, Edward P. [3 ,4 ]
Meyer-Hermann, Michael [5 ,6 ,7 ]
Victora, Gabriel D. [1 ]
机构
[1] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA
[2] Univ Paris 05, Fac Med, Inst Necker Enfants Malad, INSERM,U1151,CNRS,UMR 8253,Sorbonne Paris Cite, F-75014 Paris, France
[3] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA
[4] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA
[5] Helmholtz Ctr Infect Res, Dept Syst Immunol, Inhoffenstr 7, D-38124 Braunschweig, Germany
[6] Helmholtz Ctr Infect Res, Braunschweig Integrated Ctr Syst Biol, Inhoffenstr 7, D-38124 Braunschweig, Germany
[7] Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, D-38106 Braunschweig, Germany
基金
瑞士国家科学基金会;
关键词
PRIMARY IMMUNE-RESPONSE; IN-SITU; CLONAL SELECTION; DYNAMICS; (4-HYDROXY-3-NITROPHENYL)ACETYL; CELLS; DIVERSITY; ORIGIN; MEMORY; MYC;
D O I
10.1126/science.aad3439
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 nonimmunodominant specificities must be elicited, as is the case for HIV-1 and influenza.
引用
收藏
页码:1048 / 1054
页数:7
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