The variegated aspects of Immunoglobulin A

Although immunoglobulins (Ig) of the A isotype were discovered more than 50 years ago, their homeostatic function, production and specificity has only lately started to be unravelled. We have recently described that the level of IgAs is genetically determined and contributes to microbiota diversification via establishing a positive feedback loop of IgA production. Here we show that the amount of both fecal and serum IgAs is intermediate in a F1 BALB/c x C57BL/6 mixed background. Naïve mice that have never been exposed to certain bacterial strains but that carry innate IgAs that react towards those bacteria undergo de novo differentiation of antigen-specific responses, indicating that there is not just a recall of a pre-existing innate IgA response. We also demonstrate that, differently from pathogenic bacteria, a commensal does not induce systemic IgG response but only a mucosal IgA response. Thus IgAs come into different flavours and can potentiate their own production, but also drive the development of new specificities.