Friday, September 29, 2017

Gut IgA are naturally microbiota-reactive and polyreactive (cross-reactive)

Gut immune system naturally produces large quantities of IgA, an antibody isotype frequently found at mucosal surfaces. Since these IgA antibodies are found in mice in absence of immunization and infection they were dubbed natural and were thought to be specific for microbiota or food antigens. However a formal proof for such conclusions were lacking. 

This week journal Science published a new study from Bendelac's Lab to show that these naturally occurring IgA antibodies are present even in mice devoid of microbiota or food antigens.

In this study the authors analyzed specificity of IgA antibodies using single cell analysis. Interestingly, IgA bound to some but not to all microbiota species. 

Furthermore, most of gut IgA bound to all kind of microbiota-derived components showing a broad polyreactivity (cross-reactivity). Separate test using broadly-neutralizing antibody (bnAb) panel directed against influenza stalk region showed co-staining for microbiota coated by IgA. 

Interestingly, unlike other tissues, numbers of IgA+ plasma cells in small intestine were not reduced in germ-free mice.

Even more surprising, numbers of IgA+ plasma cells in small intestine were not reduced in germ-free mice fed antigen-free diet (amino acid diet).

These results suggest that 

(a) not all microbiota species are targeted by IgA that by itself requires further studies to understand why it is the case.

(b) natural, microbiota-reactive IgA in small intestine develop in absence of exogenous antigenic stimulation that suggests that such specificities are inherited and accumulate spontaneously. 

(c) selection of broadly neutralizing antibodies against viruses could be influenced by microbiota-derived antigens (polyreativity, cross-reactivity)  

posted by David Usharauli

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