tetano
Editor, Senior Moderator
Sci Transl Med 6 February 2013:
Vol. 5, Issue 171, p. 171ra19
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004794
Research Article
Influenza
Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination
Ning Jiang1,*,?,
Jiankui He1,*,?,
Joshua A. Weinstein2,*,?,
Lolita Penland1,
Sanae Sasaki3,4,
Xiao-Song He4,5,
Cornelia L. Dekker6,
Nai-Ying Zheng7,
Min Huang7,
Meghan Sullivan7,
Patrick C. Wilson7,
Harry B. Greenberg3,4,5,
Mark M. Davis3,8,
Daniel S. Fisher9,10 and
Stephen R. Quake1,2,8,9,?
+ Author Affiliations
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
2Biophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.
3Department of Immunology and Microbiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
5Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
6Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
7Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA.
8Howard Hughes Medical Institute.
9Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
10Department of Biology, Stanford University, Stanford, CA 94305, USA.
+ Author Notes
↵* These authors contributed equally to this work.
↵? Present address: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
↵? Present address: Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
↵? Present address: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
↵?To whom correspondence should be addressed. E-mail: quake@stanford.edu
Abstract
The human antibody repertoire is one of the most important defenses against infectious disease, and the development of vaccines has enabled the conferral of targeted protection to specific pathogens. However, there are many challenges to measuring and analyzing the immunoglobulin sequence repertoire, including that each B cell?s genome encodes a distinct antibody sequence, that the antibody repertoire changes over time, and the high similarity between antibody sequences. We have addressed these challenges by using high-throughput long read sequencing to perform immunogenomic characterization of expressed human antibody repertoires in the context of influenza vaccination. Informatic analysis of 5 million antibody heavy chain sequences from healthy individuals allowed us to perform global characterizations of isotype distributions, determine the lineage structure of the repertoire, and measure age- and antigen-related mutational activity. Our analysis of the clonal structure and mutational distribution of individuals? repertoires shows that elderly subjects have a decreased number of lineages but an increased prevaccination mutation load in their repertoire and that some of these subjects have an oligoclonal character to their repertoire in which the diversity of the lineages is greatly reduced relative to younger subjects. We have thus shown that global analysis of the immune system?s clonal structure provides direct insight into the effects of vaccination and provides a detailed molecular portrait of age-related effects.
Copyright ? 2013, American Association for the Advancement of Science
http://stm.sciencemag.org/content/5/171/171ra19
Vol. 5, Issue 171, p. 171ra19
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004794
Research Article
Influenza
Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination
Ning Jiang1,*,?,
Jiankui He1,*,?,
Joshua A. Weinstein2,*,?,
Lolita Penland1,
Sanae Sasaki3,4,
Xiao-Song He4,5,
Cornelia L. Dekker6,
Nai-Ying Zheng7,
Min Huang7,
Meghan Sullivan7,
Patrick C. Wilson7,
Harry B. Greenberg3,4,5,
Mark M. Davis3,8,
Daniel S. Fisher9,10 and
Stephen R. Quake1,2,8,9,?
+ Author Affiliations
1Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
2Biophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.
3Department of Immunology and Microbiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
5Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
6Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
7Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA.
8Howard Hughes Medical Institute.
9Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
10Department of Biology, Stanford University, Stanford, CA 94305, USA.
+ Author Notes
↵* These authors contributed equally to this work.
↵? Present address: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
↵? Present address: Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
↵? Present address: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
↵?To whom correspondence should be addressed. E-mail: quake@stanford.edu
Abstract
The human antibody repertoire is one of the most important defenses against infectious disease, and the development of vaccines has enabled the conferral of targeted protection to specific pathogens. However, there are many challenges to measuring and analyzing the immunoglobulin sequence repertoire, including that each B cell?s genome encodes a distinct antibody sequence, that the antibody repertoire changes over time, and the high similarity between antibody sequences. We have addressed these challenges by using high-throughput long read sequencing to perform immunogenomic characterization of expressed human antibody repertoires in the context of influenza vaccination. Informatic analysis of 5 million antibody heavy chain sequences from healthy individuals allowed us to perform global characterizations of isotype distributions, determine the lineage structure of the repertoire, and measure age- and antigen-related mutational activity. Our analysis of the clonal structure and mutational distribution of individuals? repertoires shows that elderly subjects have a decreased number of lineages but an increased prevaccination mutation load in their repertoire and that some of these subjects have an oligoclonal character to their repertoire in which the diversity of the lineages is greatly reduced relative to younger subjects. We have thus shown that global analysis of the immune system?s clonal structure provides direct insight into the effects of vaccination and provides a detailed molecular portrait of age-related effects.
Copyright ? 2013, American Association for the Advancement of Science
http://stm.sciencemag.org/content/5/171/171ra19