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Type: Journal article
Title: Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice
Author: Poyntz, H.
Jones, A.
Jauregui, R.
Young, W.
Gestin, A.
Mooney, A.
Lamiable, O.
Altermann, E.
Schmidt, A.
Gasser, O.
Weyrich, L.
Jolly, C.
Linterman, M.
Gros, G.
Hawkins, E.
Forbes-Blom, E.
Citation: Immunology and Cell Biology, 2019; 97(1):39-53
Publisher: Wiley
Issue Date: 2019
ISSN: 0818-9641
Statement of
Hazel C Poyntz, Angela Jones, Ruy Jauregui, Wayne Young, Aurélie Gestin ... Laura Weyrich ... et al.
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
Rights: © 2018 Malaghan Institute of Medical Research Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
RMID: 0030099497
DOI: 10.1111/imcb.12199
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Appears in Collections:Environment Institute publications

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