Age-Related Changes in Human Peripheral Blood IGH Repertoire Following Vaccination
Open Access
- 1 January 2012
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 3, 193
- https://doi.org/10.3389/fimmu.2012.00193
Abstract
Immune protection against pulmonary infections, such as seasonal flu and invasive pneumonia, is severely attenuated with age, and vaccination regimes for the elderly people often fail to elicit effective immune responses. We have previously shown that influenza and pneumococcal vaccine responses in the older population are significantly impaired in terms of serum antibody production, and have shown repertoire differences by CDR-H3 spectratype analysis. Here we report a detailed analysis of the B cell repertoire in response to vaccine, including a breakdown of sequences by class and subclass. Clustering analysis of high throughput sequencing data enables us to visualise the response in terms of expansions of clonotypes, changes in CDR-H3 characteristics, and somatic hypermutation as well as identifying the commonly used IGH genes. We have highlighted a number of significant age-related changes in the B cell repertoire. Interestingly, in light of the fact that IgG is the most prevalent serum antibody and the most widely used as a correlate of protection, the most striking age-related differences are in the IgA response, with defects also seen in the IgM repertoire. In addition there is a skewing towards IgG2 in the IgG sequences of the older samples at all time points. This analysis illustrates the importance of antibody classes other than IgG and has highlighted a number of areas for future consideration in vaccine studies of the elderly.Keywords
This publication has 42 references indexed in Scilit:
- Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestineThe Journal of Experimental Medicine, 2012
- Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodiesJournal of Clinical Investigation, 2011
- Vaccination‐induced changes in human B‐cell repertoire and pneumococcal IgM and IgA antibody at different agesAging Cell, 2011
- The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specificJournal of Clinical Investigation, 2011
- Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal VaccinationsInfection and Immunity, 2011
- B‐cell diversity decreases in old age and is correlated with poor health statusAging Cell, 2009
- IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysisNucleic Acids Research, 2008
- Rapid cloning of high-affinity human monoclonal antibodies against influenza virusNature, 2008
- Repression of BCL-6 is required for the formation of human memory B cells in vitroThe Journal of Experimental Medicine, 2007
- Insights into the Interaction between Influenza Virus and PneumococcusClinical Microbiology Reviews, 2006