Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.
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Date
2019-01-01
Open Access Location
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley and Sons Inc.
Rights
(c) 2018 Malaghan Institute of Medical Research
CC BY 4.0
CC BY 4.0
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.
Description
Keywords
Class-switch recombination, gene regulation in immune cells, humoral immunity, vaccines, Animals, Antibody Formation, B-Lymphocytes, Immunoglobulin Class Switching, Mice, Mice, Inbred BALB C, Polymorphism, Genetic, Vaccines, Whole Genome Sequencing
Citation
Poyntz HC, Jones A, Jauregui R, Young W, Gestin A, Mooney A, Lamiable O, Altermann E, Schmidt A, Gasser O, Weyrich L, Jolly CJ, Linterman MA, Gros GL, Hawkins ED, Forbes-Blom E. (2019). Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.. Immunol Cell Biol. 97. 1. (pp. 39-53).