2.50
Hdl Handle:
http://hdl.handle.net/10033/609125
Title:
Visualizing antibody affinity maturation in germinal centers.
Authors:
Tas, Jeroen M J; Mesin, Luka; Pasqual, Giulia; Targ, Sasha; Jacobsen, Johanne T; Mano, Yasuko M; Chen, Casie S; Weill, Jean-Claude; Reynaud, Claude-Agnès; Browne, Edward P; Meyer-Hermann, Michael ( 0000-0002-4300-2474 ) ; Victora, Gabriel D
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
Visualizing antibody affinity maturation in germinal centers. 2016, 351 (6277):1048-54 Science
Journal:
Science (New York, N.Y.)
Issue Date:
4-Mar-2016
URI:
http://hdl.handle.net/10033/609125
DOI:
10.1126/science.aad3439
PubMed ID:
26912368
Type:
Article
Language:
en
ISSN:
1095-9203
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorTas, Jeroen M Jen
dc.contributor.authorMesin, Lukaen
dc.contributor.authorPasqual, Giuliaen
dc.contributor.authorTarg, Sashaen
dc.contributor.authorJacobsen, Johanne Ten
dc.contributor.authorMano, Yasuko Men
dc.contributor.authorChen, Casie Sen
dc.contributor.authorWeill, Jean-Claudeen
dc.contributor.authorReynaud, Claude-Agnèsen
dc.contributor.authorBrowne, Edward Pen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.contributor.authorVictora, Gabriel Den
dc.date.accessioned2016-05-12T08:09:36Zen
dc.date.available2016-05-12T08:09:36Zen
dc.date.issued2016-03-04en
dc.identifier.citationVisualizing antibody affinity maturation in germinal centers. 2016, 351 (6277):1048-54 Scienceen
dc.identifier.issn1095-9203en
dc.identifier.pmid26912368en
dc.identifier.doi10.1126/science.aad3439en
dc.identifier.urihttp://hdl.handle.net/10033/609125en
dc.description.abstractAntibodies 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.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntibodiesen
dc.subject.meshAntibody Affinityen
dc.subject.meshB-Lymphocytesen
dc.subject.meshGerminal Centeren
dc.subject.meshHIV-1en
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshMicroscopy, Fluorescence, Multiphotonen
dc.subject.meshMolecular Imagingen
dc.subject.meshOrthomyxoviridaeen
dc.subject.meshSequence Analysis, DNAen
dc.subject.meshSingle-Cell Analysisen
dc.titleVisualizing antibody affinity maturation in germinal centers.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalScience (New York, N.Y.)en

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