Microdissected Domes from Gut-Associated Lymphoid Tissues: A Model of M Cell Transepithelial Transport In Vitro

Abstract

Specialized M cells in gut-associated lymphoid tissues (GALT) comprise 10-50% of the epithelial cell population overlying GALT domes,^1,2 and exhibit short microvilli, numerous apical vesicles, and a basolateral pocket infiltrated by clusters of lymphoid cells.^3,4 Functionally, M cells endocytose protein molecules,⁵ viruses,⁶ and Gram-microorganisms.⁷ Particle binding to the M cell apical membrane results in rapid (2 µm/min) internalization and shuttling to pocket domains and to underlying dome lymphoid tissue.⁸ While it has been shown that lymphocytes which infiltrate M cell pockets and localize to subepithelial GALT domes are MHC class II⁺ activated T cells,^4,9 and that mucosal immunization with structures which are taken up by M cells into GALT may result in the development of IgA responses,¹⁰ the relationship between M cell-mediated antigen uptake and the evolution of IgA antibody has not been examined directly. A model using microdissected domes from GALT was developed to enable the in vitro screening of a large repertoire of antigens for M cell tropism, and to study the development of IgA antibody responses to antigens recognized by M cells.