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

Immunology and Cell Biology
Hazel C PoyntzElizabeth Forbes-Blom

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 ...Continue Reading

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Citations

Aug 28, 2020·Immunology·Anne Camille La Flamme, Simon Milling
Aug 28, 2020·Immunology and Cell Biology·Simon Milling, Anne Camille La Flamme
Jan 15, 2021·Experimental Animals·Kazuyuki Mekada, Atsushi Yoshiki

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Methods Mentioned

BETA
ELISA
flow cytometry
Electrophoresis
ELISAs
PCR
Illumina sequencing
chip

Software Mentioned

ORegAnno
BBMap
UCLUST
USEARCH
Greengenes
samtools
custom Ruby script
Human splice finder
trimmomatic
GraphPad Prism

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