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  Onset of Immune Senescence Defined by Unbiased Pyrosequencing of Human Immunoglobulin mRNA Repertoires

Rubelt, F., Sievert, V., Knaust, F., Diener, C., Lim, T. S., Klipp, E., et al. (in press). Onset of Immune Senescence Defined by Unbiased Pyrosequencing of Human Immunoglobulin mRNA Repertoires. PLoS One, 11(7), e49774-e49774. doi:10.1371/journal.pone.0049774.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B888-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B889-F
Genre: Journal Article

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 Creators:
Rubelt, Florian1, Author              
Sievert, Volker2, Author              
Knaust, Florian, Author
Diener, Christian3, Author
Lim, Theam Soon4, Author
Klipp, Edda5, Author              
Reinhardt, Richard6, Author              
Lehrach, Hans1, Author
Konthur, Zoltán1, Author              
Affiliations:
1In vitro Ligand Screening (Zoltán Konthur), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 63-74, Berlin, Germany, ou_1479653              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 63-74, Berlin, Germany, ou_1433550              
3Theoretische Biophysik, Humboldt-Universität zu Berli, , Berlin, Germany, ou_persistent22              
4Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia, ou_persistent22              
5Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 63-74, Berlin, Germany, ou_1433554              
6High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 63-74, Berlin, Germany, ou_1433552              

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 Abstract: The immune system protects us from foreign substances or pathogens by generating specific antibodies. The variety of immunoglobulin (Ig) paratopes for antigen recognition is a result of the V(D)J rearrangement mechanism, while a fast and efficient immune response is mediated by specific immunoglobulin isotypes obtained through class switch recombination (CSR). To get a better understanding on how antibody-based immune protection works and how it changes with age, the interdependency between these two parameters need to be addressed. Here, we have performed an in depth analysis of antibody repertoires of 14 healthy donors representing different gender and age groups. For this task, we developed a unique pyrosequencing approach, which is able to monitor the expression levels of all immunoglobulin V(D)J recombinations of all isotypes including subtypes in an unbiased and quantitative manner. Our results show that donors have individual immunoglobulin repertoires and cannot be clustered according to V(D)J recombination patterns, neither by age nor gender. However, after incorporating isotype-specific analysis and considering CSR information into hierarchical clustering the situation changes. For the first time the donors cluster according to age and separate into young adults and elderly donors (.50). As a direct consequence, this clustering defines the onset of immune senescence at the age of fifty and beyond. The observed age-dependent reduction of CSR ability proposes a feasible explanation why reduced efficacy of vaccination is seen in the elderly and implies that novel vaccine strategies for the elderly should include the ‘‘Golden Agers’’.

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Language(s): eng - English
 Dates: 2012-11-302012-08-092012-10-12
 Publication Status: Accepted / In Press
 Pages: -
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 Identifiers: DOI: 10.1371/journal.pone.0049774
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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 11 (7) Sequence Number: - Start / End Page: e49774 - e49774 Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850