Epithelial M Cells: Gateways for Mucosal Infection and Immunization

mucosal and glandular tissues, where they differentiate and Jean-Pierre Kraehenbuhl ‡ into plasma cells. The dimeric or polymeric IgA antibod-*Department of Pediatrics ies thus produced are selectively bound by epithelial Harvard Medical School and GI Cell Biology Laboratory polymeric immunoglobulin receptors, transcytosed Children's Hospital across epithelial cells, and released into glandular and Boston, Massachusetts 02115 mucosal secretions (Apodaca et al., 1991). Thus, M cell † Center for Molecular Biology of Inflammation transcytosis is an important first step in initiation of a University of Mü nster secretory immune response. D-48149 Mü nster Although some vesicles in the M cell apical cytoplasm Federal Republic of Germany contain the endosomal protease cathepsin E, the late ‡ Swiss Institute for Experimental Cancer Research and endosome/lysosome membrane marker lgp120, and Institute for Biochemistry generate an acidic internal milieu (Allan et al., 1993), University of Lausanne antigens and microorganisms are generally delivered CH-1066 Epalinges intact and alive across M cells. This is consistent with our Switzerland demonstration that when Peyer's patch lymphoblasts of mucosally immunized mice are used to generate hybrid-The epithelia that line the vast mucosal surfaces of the omas, the resulting monoclonal antibodies are primarily gastrointestinal, respiratory, and urogenital tracts serve dimeric IgAs directed against microbial surface compo-as delicate interfaces between external environments, nents. Such antibodies are well suited to intercept intact rich in foreign antigens and microbial pathogens, and pathogens on mucosal surfaces and can be sufficient the internal environment of the mucosa. A major branch to protect against lethal doses of the corresponding of the immune system operates in mucosal tissues, pro-pathogen (Neutra et al., 1994b). viding these surfaces with protective secretory antibod-Sampling of Microorganisms by M Cells ies (McGhee et al., 1992). Sampling of luminal antigens M cell transport of enteric microorganisms seems to occurs at specialized local inductive sites (the " orga-be a key strategy for host defense, but the molecular nized mucosa-associated lymphoid tissue " or O-MALT) that appear as single or aggregated mucosal lymphoid follicles in the tonsils, adenoids, bronchi, and intestines, including the colon and rectum. For antigens to elicit mucosal immune responses, they must be transported across the epithelial barrier at these sites. This is accomplished by induction of a specialized epithelium over mucosal lymphoid follicles (the " follicle-associated epi-thelium "). The follicle-associated epithelium contains M cells, a unique epithelial cell type specialized for trans-epithelial transport of macromolecules, particles, and microorganisms (Neutra et al., 1996). M …