TY - JOUR
T1 - Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice
AU - Poyntz, Hazel C.
AU - Jones, Angela
AU - Jauregui, Ruy
AU - Young, Wayne
AU - Gestin, Aurélie
AU - Mooney, Anna
AU - Lamiable, Olivier
AU - Altermann, Eric
AU - Schmidt, Alfonso
AU - Gasser, Olivier
AU - Weyrich, Laura
AU - Jolly, Christopher J.
AU - Linterman, Michelle A.
AU - Gros, Graham Le
AU - Hawkins, Edwin D.
AU - Forbes-Blom, Elizabeth
N1 - Publisher Copyright:
© 2018 Malaghan Institute of Medical Research Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
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U2 - 10.1111/imcb.12199
DO - 10.1111/imcb.12199
M3 - Article
C2 - 30152893
AN - SCOPUS:85054918295
SN - 0818-9641
VL - 97
SP - 39
EP - 53
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
IS - 1
ER -