Architecture of intestinal TD and TI IgA responses

Architecture of intestinal TD and TI IgA responses. Antigen-sampling DCs receive conditioning signals from TLR-activated IECs through TSLP and RA and thereafter differentiate into various DC subsets releasing TGF-β, IL-10, RA, and nitric oxide. These DCs initiate TD IgA responses in Peyer’s patches by inducing TH2, Treg, and Treg-derived TFH cells that activate follicular B cells through CD40L, TGF-β, IL-4, IL-10, and IL-21. IgA-expressing B cells emerging from this TD pathway differentiate into plasma cells in mesenteric lymph nodes and lamina propria. Plasma cells release IgA dimers and IgA oligomers comprising a joining (J) chain that binds to the polymeric immunoglobulin receptor (pIgR) on the basolateral membrane of IECs. This binding triggers endocytosis of polymeric IgA, protease-mediated cleavage of pIgR, and formation of a pIgR-derived secretory component protein that remains associated with the polymeric IgA-J chain complex to form secretory IgA (SIgA). This latter traffics toward the apical membrane of IECs and ultimately gets transcytosed onto the mucosal surface, where it recognizes dietary antigens, commensal bacteria, and pathogens with both high- and low-affinity binding modes. In the lamina propria DCs and IECs can initiate TI IgA responses, including sequential switching from IgA1 to IgA2, by releasing BAFF, APRIL, and RA in response to TLR stimulation by microbial ligands. TSLP from IECs further amplifies IgA production by enhancing DC production of BAFF and APRIL. Together with RA, BAFF and APRIL from DCs and IECs can stimulate plasma cell differentiation and survival in addition to eliciting IgA CSR and production.

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Innate signals in mucosal immunoglobulin class switching. () Irene Puga, et al. J Allergy Clin Immunol. ;126(5):889-897. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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