The Inhibitory Receptor PD-1 Regulates IgA Selection and Bacterial Composition in the Gut

Gut Reaction The gut needs to keep its trillions of microbial inhabitants contained. The immune system has evolved a multifaceted approach to this problem, which includes the production of large quantities of immunoglobulin A (IgA) in the intestinal mucosa. In a process that is not well understood, plasma cells that produce IgA specific for the gut microflora are selected in Peyer's patches in the gut. Kawamoto et al. (p. 485) used genetically manipulated mice to show that the inhibitory co-receptor, programmed cell death-1 (PD-1), is required for the proper selection IgA-secreting cells in the gut. The effect of PD-1 deletion, however, was not intrinsic to the B cells that produce IgA. Instead, the absence of PD-1 affected the differentiation of T follicular helper cells, which provide important signals to B cells that help guide them as they develop the capacity to produce microflora-specific IgA. Mice deficient in PD-1 exhibited alterations in the composition in their microflora, which suggests that defective selection of IgA can perturb the careful balance that exists between the immune system and resident bacteria.