IgA and the intestinal microbiota: the importance of being specific

Secretory IgA has long been a divisive molecule. Some immunologists point to the mild phenotype of IgA deficiency to justify ignoring it, while some consider its abundance and evolutionary history as grounds for its importance. Further, there is extensive and growing disagreement over the relative importance of affinity-matured, T cell-dependent IgA vs. “natural” and T cell-independent IgA in both microbiota and infection control. As with all good arguments, there is good data supporting different opinions. Here we revisit longstanding questions in IgA biology. We start the discussion from the question of intestinal IgA antigen specificity and critical definitions regarding IgA induction, specificity, and function. These definitions must then be tessellated with the cellular and molecular pathways shaping IgA responses, and the mechanisms by which IgA functions. On this basis we propose how IgA may contribute to the establishment and maintenance of beneficial interactions with the microbiota.