Pandemic, epidemic, endemic: B cell repertoire analysis reveals unique anti-viral responses to SARS-CoV-2, Ebola and respiratory syncytial virus
Author(s)
Type
Journal Article
Abstract
Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects.
Date Issued
2022-05-03
Date Acceptance
2022-03-15
Citation
Frontiers in Immunology, 2022, 13, pp.1-15
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
15
Journal / Book Title
Frontiers in Immunology
Volume
13
Copyright Statement
© 2022 Stewart, Sinclair, Ng, O’Hare, Page, Serangeli, Margreitter, Orsenigo, Longman, Frampas, Costa, Lewis, Kasar, Wu, Kipling, Openshaw, Chiu, Baillie, Scott, Semple, Bailey, Fraternali and Dunn-Walters. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
UKRI MRC COVID-19 Rapid Response Call
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000796986100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
G0902266
MR/T50256X/1
NIHR201385
MC_PC19025
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
B cell
COVID-19
ebola
RSV (respiratory syncytial virus)
immunity
repertoire
class-switch recombination (CSR)
CLASS SWITCH RECOMBINATION
CYTIDINE DEAMINASE AID
ANTIBODY-RESPONSES
MEMORY
HYPERMUTATION
MECHANISM
INFECTION
IGM
Publication Status
Published
Article Number
ARTN 807104
Date Publish Online
2022-05-03