The immune landscape of IgA induction in the gut

Antibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.