Immunoglobulin A: a bridge between innate and adaptive immunity.

PURPOSE OF REVIEW: The review summarizes the recent progress that has been made in understanding the function of immunoglobulin A (IgA) in promoting a healthy mutualism with the commensal microbiota and protecting against pathogens. Although IgA is by far the most abundant antibody produced by mammals, direct experimental evidence for its function is still lacking. RECENT
FINDINGS: IgA is the predominant antibody induced in response to intestinal colonization with commensal bacteria: even fish have been shown to have a mucosal immunoglobulin (IgT), which is produced in the mucosa and coats commensals in the intestinal lumen. Recent studies indicate that intestinal IgA can be highly specific to the inducing commensals. Priming of IgA also appears to be a long-lasting response dependent on the overall dose (integral) of the bacteria sampled rather than exhibiting prime-boost effects normally observed with systemic immunoglobulin responses. Not only is human IgA highly mutated, but a mouse model with deficient hypermutation but intact class-switch recombination also shows that this mutation process (presumably leading to better anticommensal affinities) is important for IgA protection at the mucosal surface. It has been shown that some IgA can be induced independently of T cells through stimulation by epithelial cell and plasmacytoid dendritic cell cytokines including BAFF and APRIL, although the relative roles of the T-dependent and T-independent IgA pathways in generating mucosal protection are still unclear.
SUMMARY: Protection at mucosal surfaces through the secretion of antibodies is a phylogenetically ancient function. Mammals can produce high and low-affinity IgA against their commensal microbes via T-cell-dependent and T-cell-independent pathways to contribute to host microbial mutualism. The process of improving IgA affinity to intestinal luminal contents through somatic hypermutation of immunoglobulin genes improves the level of protection at the mucosal surface and such mutations are abundant in human IgA sequences.