The mechanisms mediating serum immunoglobulin A (IgA) responses and their potential role in protective immunity remain unknown. Wilmore and colleagues show that members of the Proteobacteria phylum in the gut of mice promote a T cell-dependent increase in serum IgA and IgA-secreting bone marrow plasma cells. A recent study suggested that individuals with IgA deficiencies may be more susceptible to sepsis. Accordingly, transfer of proteobacteria-rich microbiotia to mice conferred serum IgA-mediated protection against sepsis.