The functional interactions of commensal bacteria with intestinal secretory IgA

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Abstract
The aim of this article is to describe the immune geography of IgA induction by commensal intestinal bacteria and the underlying mechanisms of cytokine and costimulatory signalling between dendritic cells, B cells and T cells. Intestinal dendritic cells sample commensal intestinal bacteria that penetrate the epithelial layer and induce IgA+ B cells to seed the mucosa with IgA plasma cells. Constitutive secretion of retinoic acid by intestinal dendritic cells directs the specificity of the IgA class switch and homing receptor expression in Peyer's patch B cells. In-vivo experiments have shown that TGF-beta is a vital cytokine for IgA induction in vivo, and the tumour necrosis factor family members BAFF and APRIL provide key costimulatory signals. After transport through the epithelial layer secretory IgA limits penetration of commensal bacteria back through the epithelium and shapes the density of different bacterial species in the intestinal lumen. Production of IgA is an important adaptation to the presence of commensal intestinal bacteria and induction of the response is compartmentalized within the intestinal mucosal immune system. This compartmentalization allows a vigorous mucosal immune response to commensals without needing the systemic immune system to be tolerant of these organisms.