Role of Gut-Associated Lymphoreticular Tissues in Intestinal IgA Immunity

Despite the fact that intestinal IgA responses are known to be regulated by gut-associated lymphoreticular tissues (GALT), the exact sites where this regulatory network is formed are only partially understood. Our study shows that antigen-specific intestinal IgA antibodies are induced after oral immunization in mice made deficient in Peyer's patches (PP) by in utero treatment with lymphotoxin-β receptor and Ig (LTβR-Ig). These results suggest that the PP-independent pathways exist for antigen-specific intestinal IgA responses. On the other hand, postnatal LTβR-Ig-treated mice lacking isolated lymphoid follicles (ILF) were still able to produce significant mucosal IgA responses. Furthermore, mice treated with both TNF receptor p55 and Ig (TNFR55-Ig) and LTβR-Ig in utero, which lack PP and mesenteric lymph nodes (MLN) but retain intact ILF, failed to induce antigen-specific IgA responses after oral immunization. These findings demonstrated that ILF were not essential for induction of intestinal IgA responses. Interestingly, however, the IgA responses induced in the PP- or ILF- null mice were significantly lower than those seen in the control mice. Taken together, these findings suggest that aggregated lymphoid follicles residing in the intestinal lumen, e.g. PP and ILF, and draining MLN, may comprise an integrated regulatory network for the induction of maximum IgA antibody responses to orally administered antigens.