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INTRODUCTORY REVIEW: TISSUE ANTIBODIES IN EXPERIMENTAL SYSTEMS AND IN HUMAN AUTOIMMUNITY

The first reported success with fluorescent antibody as a means of identifying a native antigen in tissues seem to have been that of J. M. Marshall in 1951,’ which described the preparation of a rabbit antiserum against hog adrenocorticotropic hormone, its conjugation with fluorescien isocyanate, and the ability of the conjugate to stain basophil cells in the hog pituitary gland. In his paper, Marshall includes the following sentence: “Because the hormone was shown to react with the antibody, because the tissue is known to contain the hormone, and because in the tissue only the basophils bound antibody, it appears that the basophils must contain the adrenocorticotropic hormone.” The logic of this approach, with its initial requirement to prepare a potent antiserum and, before labeling it, to analyze and establish its specific reactivity, lies behind most successful applications of the IF method; and this is especially so in the tissue antigen field, whether our interests be in experimental systems or in the investigation of autoimmune disease. The direct system of IF staining, such as that used by Marshall, has its main attraction in tissue systems where it is desired to analyze the distribution of an antigen which can be extracted, purified, and used to immunize another species in which it is a potent immunogen. This can be the case not only for species antigens, but also for some isoantigens-those of the human A, B, H and Lea blood group antigens, for example. Thirteen years ago we used conjugated rabbit antiA, B, and Lea globulins in this way to demonstrate the distribution of these isoantigens in the mucous membranes of the gut, in the vascular endothelium, and in other sites in human tissues by simple direct staining of cryostat sections.2 Convincing success with this type of direct immunofluorescent staining depends not only upon the presence of antigen in the cells or on the membranes under examination, but also upon its concentration at these sites-how thick, as it were, antigen molecules are on the ground. One of the most important applications of direct immunofluorescence to antigenic analysis of tissues has been in the localizing of plasma proteins, and more particularly immunoglobulins, in the tissues, with the object of identifying cellular sites of formation of antibody and also tissue sites of deposition of antibody. The increasing discriminatory power of antiglobulin sera that has developed with increasing knowledge of immunoglobulin types, classes, subclasses, and groups has enabled us to identify with great precision the immunoglobulin formed by a given stained plasma cell. However, one cannot fail to be struck, on examining any population of morphological plasma cells in tissue, how a proportion always seem to be unstainable