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Science. 2016 Mar 4;351(6277):1048-54. doi: 10.1126/science.aad3439. Epub 2016 Feb 18.

Visualizing antibody affinity maturation in germinal centers.

Author information

1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
2
Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cité, Université Paris Descartes, Faculté de Médecine-Site Broussais, 75014 Paris, France.
3
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
4
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstraβe7, 38124 Braunschweig, Germany. Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany.
5
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. victora@wi.mit.edu.

Abstract

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.

PMID:
26912368
PMCID:
PMC4938154
DOI:
10.1126/science.aad3439
[Indexed for MEDLINE]
Free PMC Article

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