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

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Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory. / Burton, Bronwen R; Tennant, Richard K; Love, John; Titball, Richard W; Wraith, David C; White, Harry N.

In: Elife, Vol. 7, e26832, 01.05.2018.

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Burton, Bronwen R ; Tennant, Richard K ; Love, John ; Titball, Richard W ; Wraith, David C ; White, Harry N. / Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory. In: Elife. 2018 ; Vol. 7.

Bibtex

@article{31a521c19c1146dfa2aed74320197c2a,
title = "Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory",
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.",
keywords = "Journal Article",
author = "Burton, {Bronwen R} and Tennant, {Richard K} and John Love and Titball, {Richard W} and Wraith, {David C} and White, {Harry N}",
note = "{\textcopyright} 2018, Burton et al.",
year = "2018",
month = may,
day = "1",
doi = "10.7554/eLife.26832",
language = "English",
volume = "7",
journal = "Elife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

T1 - Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory

AU - Burton, Bronwen R

AU - Tennant, Richard K

AU - Love, John

AU - Titball, Richard W

AU - Wraith, David C

AU - White, Harry N

N1 - © 2018, Burton et al.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.7554/eLife.26832

DO - 10.7554/eLife.26832

M3 - Article

C2 - 29709214

VL - 7

JO - Elife

JF - Elife

SN - 2050-084X

M1 - e26832

ER -