Immunohistochemical studies of the immunoglobulin-producing cell systems of the human intestinal mucosa

Since the reliability of immunohistochemical observations is highly dependent on the quality of the immunological reagents, the importance of purification, characterization and performances testing of the fluorochrome conjugates is discussed. The methods of tissue processing, immunohistochemical staining and differential enumeration of fluorescing cells used in our laboratory are described. The normal intestinal mucosa shows a striking preponderance (80-90%) of IgA immunocytes, and these cells produce J chains which are incorporated into dimeric IgA. The dimers are taken up by the columnar epithelial cells which produce "secretory component" (SC). Complexing of dimeric IgA with SC seems to explain the selective transport of IgA through the crypt epithelium. A similar transport mechanism operates for J-chain-containing pentameric IgM. Marked alterations of the intestinal immunocyte populations are seen associated with various bowel diseases. In coeliac disease and dermatitis herpetiformis, a numerical increase takes place for all Ig-producing cell classes--in relative terms most prominent for IgG and IgM cells. In ulcerative colitis and Crohn's disease, the IgG-cell response is very striking, In alpha-chain disease, the lamina propria is infiltrated with IgA cells that lack light-chain-producing capacity but show some ability to synthesize J chains; dimers of alpha chain are hence transported to the intestinal lumen but cannot function as antibodies. In patients with a complete and selective lack of IgA in serum, IgA-producing cells are absent from the intestinal mucosa, and there is a numerical increase of local IgG- and specially IgM-producing cells. Conversely, patients with a partial deficiency of serum IgA may show a fairly normal intestinal IgA-cell population, although the proportion of IgM-producing cells is often increased. The intestinal mucosa of patients with a generalized hypogrammaglobulinaemia is sometimes devoid of plasma cells, but rare Ig-producing immunocytes, especially of the IgM class, are often seen. Supported in part by the Norwegian Research Council for Science and the Humanities, Anders Jahres Fond, and Helga Sembs fond. We thank Ms. Evy Eriksen and Ms. Gummvor Oijordbakken for technical assistance, and Ms. Liv Støottum for typing the manuscript.