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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., Skriner, K., et al. (2012). Onset of immune senescence defined by unbiased pyrosequencing of human immunoglobulin mRNA repertoires. PLoS One, 7(11): e49774. doi:10.1371/journal.pone.0049774.

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© 2012 Rubelt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Rubelt, F.1, Autor           
Sievert, V.2, Autor           
Knaust, F., Autor
Diener, C., Autor
Lim, T. S., Autor
Skriner, K., Autor
Klipp, E., Autor
Reinhardt, R.3, 4, Autor           
Lehrach, H.2, Autor           
Konthur, Z.1, Autor           
Affiliations:
1In vitro Ligand Screening (Zoltán Konthur), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479653              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433550              
3High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1433552              
4Max Planck Genome Centre Cologne, Max Planck Institute for Plant Breeding Research, Cologne, Germany, ou_persistent22              

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 Zusammenfassung: 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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 Datum: 2012-11-302012
 Publikationsstatus: Erschienen
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1371/journal.pone.0049774
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Titel: PLoS One
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: San Francisco, CA : Public Library of Science
Seiten: - Band / Heft: 7 (11) Artikelnummer: e49774 Start- / Endseite: - Identifikator: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850