Visualizing antibody affinity maturation in germinal centers.

Science
Authors
Keywords
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.

Year of Publication
2016
Journal
Science
Volume
351
Issue
6277
Pages
1048-54
Date Published
2016 Mar 04
ISSN
1095-9203
URL
DOI
10.1126/science.aad3439
PubMed ID
26912368
PubMed Central ID
PMC4938154
Links
Grant list
DP5 OD012146 / OD / NIH HHS / United States
S10 OD016326 / OD / NIH HHS / United States
5DP5OD012146 / OD / NIH HHS / United States