Tango of B cells with T cells in the making of secretory antibodies to gut bacteria

Polymeric IgA and IgM are transported across the epithelial barrier from plasma cells in the lamina propria to exert a function in the gut lumen as secretory antibodies. Many secretory antibodies are reactive with the gut bacteria, and mounting evidence suggests that these antibodies are important for the host to control gut bacterial communities. However, we have incomplete knowledge of how bacteria-reactive secretory antibodies are formed. Antibodies from gut plasma cells often show bacterial cross-species reactivity, putting the degree of specificity behind anti-bacterial antibody responses into question. Such cross-species reactive antibodies frequently recognize non-genome-encoded membrane glycan structures. On the other hand, the T cell epitopes are peptides encoded in the bacterial genomes, thereby allowing a higher degree of predictable specificity on the T cell side of anti-bacterial immune responses. In this Perspective, we argue that the production of bacteria-reactive secretory antibodies is mainly controlled by the antigen specificity of T cells, which provide help to B cells. To be able to harness this system (for instance, for manipulation with vaccines), we need to obtain insight into the bacterial epitopes recognized by T cells in addition to characterizing the reactivity of the antibodies.