title: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Jeroen M J
authors.initials: JM
authors.lastname: Tas
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Luka
authors.initials: L
authors.lastname: Mesin
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Pasqual
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Sasha
authors.initials: S
authors.lastname: Targ
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.|Department of Immunology, Oslo University Hospital, Oslo, Norway.
authors.forename: Johanne T
authors.initials: JT
authors.lastname: Jacobsen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Yasuko M
authors.initials: YM
authors.lastname: Mano
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Casie S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cité, Université Paris Descartes, Faculté de Médecine-Site Broussais, 75014 Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
authors.affiliation: Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cité, Université Paris Descartes, Faculté de Médecine-Site Broussais, 75014 Paris, France.
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
authors.affiliation: 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.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Browne
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer-Hermann
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. victora@wi.mit.edu.
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Victora
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D057054:Molecular Imaging / Q000379:methods*; D009975:Orthomyxoviridae / Q000276:immunology; D017422:Sequence Analysis, DNA; D059010:Single-Cell Analysis
chemical_list: D000906:Antibodies