Visualizing antibody affinity maturation in germinal centers

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / immunology*
  • Antibody Affinity / genetics
  • Antibody Affinity / immunology*
  • B-Lymphocytes / immunology*
  • Germinal Center / immunology*
  • HIV-1 / immunology
  • Humans
  • Mice
  • Microscopy, Fluorescence, Multiphoton
  • Molecular Imaging / methods*
  • Orthomyxoviridae / immunology
  • Sequence Analysis, DNA
  • Single-Cell Analysis


  • Antibodies