![]() ![]() ![]() Immunolgobulins recognize antigens via paratopes primarily defined by complementarity determining regions (CDRs). Schematic illustration of immunoglobulin G in complex with antigen and mechanism of V(D)J recombination, as well as amplification strategy for 454-sequencing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.įigure 1. TSL acknowledges financial support from the Malaysia Ministry of Higher Education, Higher Institution Center of Excellence (HICoE) Grant (311/CIPPM/4401005). 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.įunding: This work was supported by Max Planck Society for the Advancement of Sciences. Received: AugAccepted: OctoPublished: November 30, 2012Ĭopyright: © 2012 Rubelt et al. University of Medicine and Dentistry of New Jersey - New Jersey Medical School, United States of America (2012) Onset of Immune Senescence Defined by Unbiased Pyrosequencing of Human Immunoglobulin mRNA Repertoires. 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”.Ĭitation: Rubelt F, Sievert V, Knaust F, Diener C, Lim TS, Skriner K, et al. As a direct consequence, this clustering defines the onset of immune senescence at the age of fifty and beyond. For the first time the donors cluster according to age and separate into young adults and elderly donors (>50). However, after incorporating isotype-specific analysis and considering CSR information into hierarchical clustering the situation changes. 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. 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. Here, we have performed an in depth analysis of antibody repertoires of 14 healthy donors representing different gender and age groups. 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. 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). The immune system protects us from foreign substances or pathogens by generating specific antibodies. ![]()
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