Binding and transepithelial transport of immunoglobulins by intestinal M cells: demonstration using monoclonal IgA antibodies against enteric viral proteins.

Abstract

Abstract. M cells of intestinal epithelia overlying lymphoid follicles endocytose luminal macromolecules and microorganisms and deliver them to underlying lymphoid tissue. The effect of luminal secretory IgA antibodies on adherence and transepithelial transport of antigens and microorganisms by M cells is unknown. We have studied the interaction of monoclonal IgA antibodies directed against specific enteric viruses, or the hapten trinitrophenyl (TNP), with M cells. To produce monospecific IgA antibodies against mouse mammary tumor virus (MMTV) and reovirus type 1, Peyer's patch cells from mucosally immunized mice were fused with myeloma cells, generating hybridomas that secreted virus-specific IgA antibodies in monomeric and polymeric forms. One of two anti-MMTV IgA antibodies specifically bound the viral surface glycoprotein gp52, and 3 of 10 antireovirus IgA antibodies immunoprecipitated sigma 3 and mu lc surface proteins. 35S-labeled IgA antibodies injected intravenously into rats were recovered in bile as higher toolecular weight species, suggesting that secretory component had been added on passage through the liver. Radiolabeled or colloidal gold-conjugated mouse IgA was injected into mouse, rat, and rabbit intestinal loops containing Peyer's patches. Light microscopic autoradiography and EM showed that all IgA antibodies (antivirus or anti-TNP) bound to M cell luminal membranes and were transported in vesicles across M cells. IgA-gold binding was inhibited by excess unlabeled IgA, indicating that binding was specific. IgGgold also adhered to M cells and excess unlabeled IgG inhibited IgA-gold binding; thus binding was not isotype-specific. Immune complexes consisting of monoclonal anti-TNP IgA and TNP-ferritin adhered selectively to M cell membranes, while TNP-ferritin alone did not. These results suggest that selective adherence of luminal antibody to M cells may facilitate delivery of virus-antibody complexes to mucosal l~m-phoid tissue, enhancing subsequent secretory immune responses or facilitating viral invasion.

New age adjuvants and delivery systems for subunit vaccines

“…Monoclonal IgA, polyclonal secretory IgA and IgA antigen complexes were shown to adhere selectively to M cell surfaces and transported into the intraepithelial pocket (96). In this way slgA would serve as a vaccine-targeting molecule.…”

Distribution of Monoclonal Antibodies in Intestinal and Urogenital Secretions of Mice Bearing Hybridoma ‘Backpack’ Tumours

“…IgA hybridomas are first generated from Peyer's patch lymphoblasts after mucosal immunization of BALB/c mice, and clones are selected for appropriate antimicrobial antigen specificities and for efficient production of dimeric IgA monoclonal antibodies in culture [10]. The hybridoma cells are injected subcutaneously on the upper backs of naive, syngeneic mice where they grow to form hybridoma tumours that release monoclonal, dimeric IgA into the circulation.…”

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

“…SIgA exhibits the striking feature to adhere to the apical membrane of M cells (49,50), promoting uptake of small amounts of Ab as reflected by the detection of gold-coated SIgA in the pocket of M cells (51). Refined analysis of the interaction of M cells with Ab molecules demonstrated that IgA, with or without bound SC, but not IgG or IgM, bound selectively to murine and human M cells (52).…”