IgA isotype restriction in the mucosal but not in the extramucosal immune response after oral immunizations with cholera toxin or cholera B subunit

Abstract

Intestinal mucosal as well as extramucosal antibody responses were studied in mice after peroral immunizations with cholera toxin or cholera B subunit. The immunizations with cholera toxin gave rise to a marked response with antitoxin-secreting cells (PFC) in Peyer's patches (PP), mesenteric lymph nodes (MLN) and spleen showing isotype distribution of IgG greater than IgA greater than IgM and with PFC kinetics in MLN and spleen that suggested migration of cells from PP after peroral administration rather than cells stimulated in situ by adsorbed antigen. Highest numbers of PFC were obtained after 2 immunizations, and further administrations resulted in a decrease in the PFC response in MLN and spleen, while the PP responsiveness was relatively unchanged, and interestingly, protective immunity and IgA-dominated antitoxin titers in intestinal washings increased markedly by the additional boosters. Animals immunized with cholera B subunit, which lacks the adenylate cyclase-stimulating capacity of cholera toxin, showed similar PFC responses in extramucosal organs as those receiving cholera toxin but were poorly protected and had correspondingly lower IgA antitoxin titers in intestinal washings. These results suggest that the mucosal IgA antitoxin predominance is mainly due to regulatory mechanisms operating on the end-stage differentiation of the committed B cells in lamina propria and that this differentiation, as judged from the different results with cholera toxin and its B subunit, might be influenced by cyclic AMP.