Binding and Transepithelial Transport of Immunoglobulins by Intestinal M Cells: Demonstration Using Monoclonal IgA Antibodies Against Enteric Viral Proteins
Overview
Affiliations
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 molecular 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. IgG-gold 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 lymphoid tissue, enhancing subsequent secretory immune responses or facilitating viral invasion.
Immunoglobulin A Antibodies: From Protection to Harmful Roles.
Gleeson P, Camara N, Launay P, Lehuen A, Monteiro R Immunol Rev. 2024; 328(1):171-191.
PMID: 39578936 PMC: 11659943. DOI: 10.1111/imr.13424.
More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis.
Frey A, Lunding L, Ehlers J, Weckmann M, Zissler U, Wegmann M Front Immunol. 2020; 11:761.
PMID: 32411147 PMC: 7198799. DOI: 10.3389/fimmu.2020.00761.
Graversen K, Bahl M, Larsen J, Ballegaard A, Rask Licht T, Bogh K Front Microbiol. 2020; 11:496.
PMID: 32292395 PMC: 7135894. DOI: 10.3389/fmicb.2020.00496.
B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.
Wallace C, Wu B, Salem M, Ansa-Addo E, Metelli A, Sun S JCI Insight. 2018; 3(7).
PMID: 29618665 PMC: 5928869. DOI: 10.1172/jci.insight.99863.
Eosinophils in mucosal immune responses.
Travers J, Rothenberg M Mucosal Immunol. 2015; 8(3):464-75.
PMID: 25807184 PMC: 4476057. DOI: 10.1038/mi.2015.2.