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

Hazel C. Poyntz, Angela Jones, Ruy Jauregui, Wayne Young, Aurélie Gestin, Anna Mooney, Olivier Lamiable, Eric Altermann, Alfonso Schmidt, Olivier Gasser, Laura Weyrich, Christopher J. Jolly, Michelle A. Linterman, Graham Le Gros, Edwin D. Hawkins, Elizabeth Forbes-Blom

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)39-53
Number of pages15
JournalImmunology and Cell Biology
Volume97
Issue number1
DOIs
StatePublished - Jan 2019

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Immunization
Antibodies
Immunoglobulin Class Switching
Antibody Formation
Vaccines
Humoral Immunity
B-Lymphocytes
Immunoglobulin G
Phenotype
Genetic Research
Genetic Recombination
Immunity
Genome
Antigens
Population
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Poyntz, H. C., Jones, A., Jauregui, R., Young, W., Gestin, A., Mooney, A., ... Forbes-Blom, E. (2019). Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice. Immunology and Cell Biology, 97(1), 39-53. https://doi.org/10.1111/imcb.12199
Poyntz, Hazel C. ; Jones, Angela ; Jauregui, Ruy ; Young, Wayne ; Gestin, Aurélie ; Mooney, Anna ; Lamiable, Olivier ; Altermann, Eric ; Schmidt, Alfonso ; Gasser, Olivier ; Weyrich, Laura ; Jolly, Christopher J. ; Linterman, Michelle A. ; Gros, Graham Le ; Hawkins, Edwin D. ; Forbes-Blom, Elizabeth. / Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice. In: Immunology and Cell Biology. 2019 ; Vol. 97, No. 1. pp. 39-53.
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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', Immunology and Cell Biology, vol. 97, no. 1, pp. 39-53. https://doi.org/10.1111/imcb.12199

Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice. / Poyntz, Hazel C.; Jones, Angela; Jauregui, Ruy; Young, Wayne; Gestin, Aurélie; Mooney, Anna; Lamiable, Olivier; Altermann, Eric; Schmidt, Alfonso; Gasser, Olivier; Weyrich, Laura; Jolly, Christopher J.; Linterman, Michelle A.; Gros, Graham Le; Hawkins, Edwin D.; Forbes-Blom, Elizabeth.

In: Immunology and Cell Biology, Vol. 97, No. 1, 01.2019, p. 39-53.

Research output: Contribution to journalArticle

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AU - Jones, Angela

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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

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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.

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