Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice

Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/imcb.12199
Journal or Publication Title: Immunology and Cell Biology
Volume: 97
Number: 1
Page Range: pp. 39-53
Date: 2018
Subjects: Fields of Research > 11 MEDICAL AND HEALTH SCIENCES > 1108 MEDICAL MICROBIOLOGY > 110899 Medical Microbiology not elsewhere classified
11 MEDICAL AND HEALTH SCIENCES > 1108 MEDICAL MICROBIOLOGY > 110899 Medical Microbiology not elsewhere classified
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1111/imcb.12199
ISSN: 08189641
Date Deposited: 21 Dec 2020 05:49
Abstract:

Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy. Here, we report diverse antibody responsiveness to unadjuvanted as well as adjuvanted immunization in substrains of BALB/c mice, resulting in high and low antibody response phenotypes. Furthermore, these antibody phenotypes were not affected by changes in environmental factors such as the gut microbiota composition. Antigen-specific B cells following immunization had a marked difference in capability to class switch, resulting in perturbed IgG isotype antibody production. In vitro, a B-cell intrinsic defect in the regulation of class-switch recombination was identified in mice with low IgG antibody production. Whole genome sequencing identified polymorphisms associated with the magnitude of antibody produced, and we propose candidate genes that may regulate isotype class-switching capability. This study highlights that mice sourced from different vendors can have significantly altered humoral immune response profiles, and provides a resource to interrogate genetic regulators of antibody responsiveness. Together these results further our understanding of immune heterogeneity and suggest additional research on the genetic influences of adjuvanted vaccine strategies is warranted for enhancing vaccine efficacy.

Keywords: Class-switch recombination; gene regulation in immune cells; humoral immunity; vaccines.

© 2018 Malaghan Institute of Medical Research Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.

Creators:
Creators
Email
Poyntz, Hazel C
UNSPECIFIED
Jones, Angela
UNSPECIFIED
Jauregui, Ruy
UNSPECIFIED
Young, Wayne
UNSPECIFIED
Gestin, Aurélie
UNSPECIFIED
Mooney, Anna
UNSPECIFIED
Lamiable, Olivier
UNSPECIFIED
Altermann, Eric
UNSPECIFIED
Schmidt, Alfonso
UNSPECIFIED
Gasser, Olivier
UNSPECIFIED
Weyrich, Laura
UNSPECIFIED
Jolly, Christopher J
UNSPECIFIED
Linterman, Michelle A
UNSPECIFIED
Gros, Graham Le
UNSPECIFIED
Hawkins, Edwin D
UNSPECIFIED
Forbes-Blom, Elizabeth
UNSPECIFIED
Last Modified: 19 Mar 2021 04:43
URI: https://eprints.centenary.org.au/id/eprint/324

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