Unknown

Dataset Information

0

High microbiota reactivity of adult human intestinal IgA requires somatic mutations.


ABSTRACT: The gut is home to the body's largest population of plasma cells. In healthy individuals, IgA is the dominating isotype, whereas patients with inflammatory bowel disease also produce high concentrations of IgG. In the gut lumen, secretory IgA binds pathogens and toxins but also the microbiota. However, the antigen specificity of IgA and IgG for the microbiota and underlying mechanisms of antibody binding to bacteria are largely unknown. Here we show that microbiota binding is a defining property of human intestinal antibodies in both healthy and inflamed gut. Some bacterial taxa were commonly targeted by different monoclonal antibodies, whereas others selectively bound single antibodies. Interestingly, individual human monoclonal antibodies from both healthy and inflamed intestines bound phylogenetically unrelated bacterial species. This microbiota cross-species reactivity did not correlate with antibody polyreactivity but was crucially dependent on the accumulation of somatic mutations. Therefore, our data suggest that a system of affinity-matured, microbiota cross-species-reactive IgA is a common aspect of SIgA-microbiota interactions in the gut.

SUBMITTER: Kabbert J 

PROVIDER: S-EPMC7526496 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

High microbiota reactivity of adult human intestinal IgA requires somatic mutations.

Kabbert Johanna J   Benckert Julia J   Rollenske Tim T   Hitch Thomas C A TCA   Clavel Thomas T   Cerovic Vuk V   Wardemann Hedda H   Pabst Oliver O  

The Journal of experimental medicine 20201101 11


The gut is home to the body's largest population of plasma cells. In healthy individuals, IgA is the dominating isotype, whereas patients with inflammatory bowel disease also produce high concentrations of IgG. In the gut lumen, secretory IgA binds pathogens and toxins but also the microbiota. However, the antigen specificity of IgA and IgG for the microbiota and underlying mechanisms of antibody binding to bacteria are largely unknown. Here we show that microbiota binding is a defining property  ...[more]

Similar Datasets

| S-EPMC5790183 | biostudies-literature
| S-EPMC4049932 | biostudies-literature
| S-EPMC5989058 | biostudies-literature
| S-EPMC5084875 | biostudies-literature
| S-EPMC8285510 | biostudies-literature
2022-09-02 | GSE175637 | GEO
| S-EPMC4533878 | biostudies-literature
| S-EPMC2780781 | biostudies-literature
2022-09-02 | GSE175609 | GEO
2022-09-02 | GSE175635 | GEO