Influence of repeated local stimulation on the splenic response to mucosal and parenteral immunization

It has been suggested that a regional immune response may be induced by local administration of small doses of antigen, whereas larger doses are capable of inducing not only a local but also a systemic immune response. Except with fluorescence, the study at the cellular level and in the mucosa of specific antibody-producing cells appears difficult. The circulation in the body of lymphocytes from the lamina propria of the gut allows the detection of antibody-producing cells in extra-intestinal lymphoid tissues. The administration of 4 times 10-9 sheep red blood cells (SRBC) by gastric intubation to BALB/c mice (repeated daily for 4 days) was found to cause the appearance in the spleen of plaque-forming cells which predominantly belonged to the IgA class and whose numbers reached a maximum at about day 8 or 9 after the onset of the immunization. This observation is relevant to splenic colonies from cells that had received their antigenic stimulation in the gut wall and thence had seeded out in the body. Booster administration of SRBC performed 3 months after the first antigenic contact induced in the spleen an immunological response similar to that observed in newly primed mice and in no way suggestive of immunologic memory. A secondary response is completely absent when the second intragastric immunization is initiated 10 days after the end of the first. The parenteral administration of 2 times 10-8 SRBC to mice primed by the oral route 15 days earlier is followed by a marked hyporeactivity of the spleen. In any case, the IgA system appears endowed with only a minimum, if any, immunological memory to non-living antigen. In some conditions local immunological stimulation may even cause tolerance.