Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA

Humoral immune responses at mucosal surfaces have historically focused on IgA. Growing evidence highlights the complexity of IgA-inducing pathways and the functional impact of IgA on mucosal commensal bacteria. In the gut, IgA contributes to the establishment of a mutualistic host–microbiota relationship that is required to maintain homeostasis and prevent disease. This Review discusses how mucosal IgA responses occur in an increasingly complex humoral defence network that also encompasses IgM, IgG and IgD. Aside from integrating the protective functions of IgA, these hitherto neglected mucosal antibodies may strengthen the communication between mucosal and systemic immune compartments. This Review considers how IgA operates alongside IgM, IgG and IgD to provide immune protection and promote homeostasis at mucosal tissue sites. The authors highlight how some of these neglected mucosal antibody isotypes may strengthen the communication between the mucosal and systemic immune compartments.