Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory
- University of Bristol, United Kingdom
- University of Exeter, United Kingdom
- University of Birmingham, United Kingdom
Abstract
Vaccines induce memory B-cells that provide high affinity secondary antibody responses to identical antigens. Memory B-cells can also re-instigate affinity maturation, but how this happens against antigenic variants is poorly understood despite its potential impact on driving broadly protective immunity against pathogens such as Influenza and Dengue. We immunised mice sequentially with identical or variant Dengue-virus envelope proteins and analysed antibody and germinal-centre (GC) responses. Variant protein boosts induced GC with higher proportions of IgM+ B-cells. The most variant protein re-stimulated GCs with the highest proportion of IgM+ cells with the most diverse, least mutated V-genes and with a slower but efficient serum antibody response. Recombinant antibodies from GC B-cells showed a higher affinity for the variant antigen than antibodies from a primary response, confirming a memory origin. This reveals a new process of antibody memory, that IgM memory cells with fewer mutations participate in secondary responses to variant antigens, demonstrating how the hierarchical structure of B-cell memory is used and indicating the potential and limits of cross-reactive antibody based immunity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided where only average values are plotted.
Article and author information
Author details
Funding
Wellcome Trust (100115/Z/12/Z)
- Harry N White
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were done following the ARRIVE guidelines under authority of UK Home Office license PPL 30/3089, with permission from University of Exeter, UK, local animal welfare ethical review board. Blood samples were taken under Ketamine and Xylazine anaesthesia and every effort was made to minimise suffering.
Copyright
© 2018, Burton et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory
eLife 7:e26832.
https://doi.org/10.7554/eLife.26832
