Intestinal IgA synthesis: regulation of front-line body defences

Key Points Intestinal immunoglobulin A (IgA) + plasma cells are derived from conventional B2 cells located in the Peyer's patches or isolated lymphoid follicles of the gut, and from B1 cells, which reside in the body cavities, in particular the peritoneal cavity. CCL25 is produced by the small intestine epithelium and specifically attracts IgA-committed B cells derived from conventional B2 cells. The presence of IgM + B cells and IgA + plasma cells in the gut depends on interactions between lymphotoxin (LT) and LTβ receptor, which are present on lymphocytes and lamina-propria stromal cells, respectively. IgM + B cells switch to IgA + B cells and differentiate to IgA + plasma cells in situ in the lamina propria, with the help of local dendritic cells and stromal cells. The presence of somatically mutated IgAs is essential for the maintenance of gut homeostasis. AID-deficient mice develop hyperplasia of isolated lymphoid follicles, which is triggered by a large increase in the number of anaerobic bacteria in the small intestine. Dysregulation of the gut flora causes activation of all the immune systems of the body. Immunoglobulin A is the most abundant immunoglobulin isotype in mucosal secretions. In this review, we summarize recent advances in our understanding of the sites, mechanisms and functions of intestinal IgA synthesis in mice. On the basis of these recent findings, we propose an updated model for the induction and regulation of IgA responses in the gut. In addition, we discuss new insights into the role of IgA in the maintenance of gut homeostasis and into the reciprocal interactions between gut B cells and the bacterial flora.