Publication Date:
2016-02-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tas, Jeroen M J -- Mesin, Luka -- Pasqual, Giulia -- Targ, Sasha -- Jacobsen, Johanne T -- Mano, Yasuko M -- Chen, Casie S -- Weill, Jean-Claude -- Reynaud, Claude-Agnes -- Browne, Edward P -- Meyer-Hermann, Michael -- Victora, Gabriel D -- 5DP5OD012146/OD/NIH HHS/ -- S10 OD016326/OD/NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 4;351(6277):1048-54. doi: 10.1126/science.aad3439. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. ; Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Sorbonne Paris Cite, Universite Paris Descartes, Faculte de Medecine-Site Broussais, 75014 Paris, France. ; 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. ; Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstrabetae7, 38124 Braunschweig, Germany. Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universitat Braunschweig, Braunschweig, Germany. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. victora@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912368" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
