Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory

Research output: Contribution to journalArticle

Authors

  • Bronwen R Burton
  • Richard K Tennant
  • John Love
  • Richard W Titball
  • Harry N White

Colleges, School and Institutes

External organisations

  • BRISTOL UNIVERSITY
  • University of Exeter

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.

Details

Original languageEnglish
Article numbere26832
JournalElife
Volume7
Early online date1 May 2018
Publication statusE-pub ahead of print - 1 May 2018

Keywords

  • Journal Article