Ultrastructural Identification of Possible Sites of Antigen Processing in Macrophages

Fishman and co-workers first suggested that the primary immune response requires the sequential interaction of antigen and two distinct cell types (1–3). This concept was supported by the finding that an RNA fraction (perhaps containing antigen and/or antigenic fragments) from antigen-stimulated macrophages was capable of inducing specific antibody production in vitro (2–5). To this time, there has been no ultrastructural evidence to elucidate the intracellular site of this antigen “processing,” or the mode of transfer of “processed,”, immunogenic material from macrophages to immunocompetent lymphoid cells. On the contrary, cell biologists, using colloidal gold (6), carbohydrates (7), hemoglobin (8), bovine serum albumin (9), Salmonella adelaide flagella (10) and T2 phage (11), have shown that following uptake by mononuclear phagocytes, these materials enter lysosomes where rapid degradation occurs. The lysosomal compartment seems an unlikely site for antigen to react with or stimulate the formation of immunogenic RNA.