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Visualizing antibody affinity maturation in germinal centers.

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.

SUBMITTER: Tas JM

PROVIDER: S-EPMC4938154 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Visualizing antibody affinity maturation in germinal centers.

Tas Jeroen M J JM Mesin Luka L Pasqual Giulia G Targ Sasha S Jacobsen Johanne T JT Mano Yasuko M YM Chen Casie S CS Weill Jean-Claude JC Reynaud Claude-Agnès CA Browne Edward P EP Meyer-Hermann Michael M Victora Gabriel D GD

Science (New York, N.Y.) 20160218 6277

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 dispa ...[more]

PMID: 26912368

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Project description:Long primed germinal centers with enduring affinity maturation and clonal migration

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