Intra-intestinal priming leads to antigen-specific IgA memory cells in peripheral lymphoid organs

The aim of this study was to gain more insight into the mechanism of IgA memory formation by testing the effects of intra-intestinal antigen priming on various booster routes. To obtain a primary immune response trinitrophenyl conjugated keyhole limpet haemocyanin (KLH-TNP) was injected into the lumen of the small intestines of mice. For secondary immune responses mice were boosted intra-intestinally, intravenously or subcutaneously. The distribution of antigen specific cells in situ was demonstrated by enzyme histochemistry whereas quantification of TNP-specific cells was performed with a plaque-forming cell assay. After single or repeated intra-intestinal antigen administrations both primary and secondary immune responses in terms of specific antibody containing cells were mainly located in the spleen. The anti-TNP antibody-containing cells produced predominantly IgM during the primary and IgM, IgG and IgA during the secondary response. In mesenteric lymph nodes and villi antigen-specific cells were detected sporadically. When intra-intestinal priming was followed by intravenous or subcutaneous booster injections most anti-TNP antibody-producing cells were demonstrated in the spleen and in the draining popliteal lymph nodes. In contrast to repeated intravenous or subcutaneous immunizations alone, these organs contained, besides specific IgM and IgG cells, many TNP-specific cells producing IgA antibodies. This result demonstrates that the production of IgA antibodies is not restricted to mucosa-associated lymphoid tissues. IgA memory cells are induced in mucosa associated lymphoid tissues, probably in Peyer's patches, will consecutively migrate throughout the whole lymphoid system and can be triggered by renewed antigen contact to become IgA plasma cells.