Selective adherence of IgA to murine Peyer's patch M cells: evidence for a novel IgA receptor.
M cells represent the primary route by which mucosal Ags are transported across the intestinal epithelium and delivered to underlying gut-associated lymphoid tissues. In rodents and rabbits, Peyer's patch M cells selectively bind and endocytose secretory IgA (SIgA) Abs. Neither the nature of the M cell IgR nor the domains of SIgA involved in this interaction are known. Using a mouse ligated ileal loop assay, we found that monoclonal IgA Abs with or without secretory component, but not IgG or IgM Abs, bound to the apical surfaces of Peyer's patch M cells, indicating that the receptor is specific for the IgA isotype. Human serum IgA and colostral SIgA also bound to mouse M cells. The asialoglycoprotein receptor or other lectin-like receptors were not detected on the apical surfaces of M cells. We used recombinant human IgA1 and human IgA2 Abs and domain swapped IgA/IgG chimeras to determine that both domains Calpha1 and Calpha2 are required for IgA adherence to mouse Peyer's patch M cells. This distinguishes the M cell IgA receptor from CD89 (FcalphaI), which binds domains Calpha2-Calpha3. Finally, we observed by immunofluorescence microscopy that some M cells in the human ileum are coated with IgA. Together these data suggest that mouse, and possibly human, M cells express an IgA-specific receptor on their apical surfaces that mediates the transepithelial transport of SIgA from the intestinal lumen to underlying gut-associated organized lymphoid tissues.
Mantis
Nicholas J
NJ
Department of Pediatrics, Harvard Medical School, and Gastrointestinal Cell Biology Laboratory, Children's Hospital, Boston, MA 02115, USA. nicholas.mantis@tch.harvard.edu
Cheung
Marsha C
MC
Chintalacharuvu
Koteswara R
KR
Rey
Jacques
J
Corthésy
Blaise
B
Neutra
Marian R
MR
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001665:Binding Sites; D004705:Endocytosis; D005260:Female; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; C045281:IgA receptor; D007071:Immunoglobulin A, Secretory; D011956:Receptors, Cell Surface; D011961:Receptors, Fc