GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO : III. INDUCTION OF SECONDARY RESPONSE AT DIFFERENT INTERVALS AFTER THE PRIMARY; THE ROLE OF SECONDARY NODULES IN THE PREPARATION FOR THE SECONDARY RESPONSE

Antibody formation in vitro by red and white pulp of the spleen and by bone marrow tissue was studied at various days after an intravenous booster injection of soluble antigens such as ovalbumin and bovine gamma globulin (BGG). When the booster injection of antigen was given early (10 days) after an intravenous primary injection, high antibody formation could be demonstrated in the spleen primarily 2 to 3 days after the injection, but much less afterwards. When the booster injection was given later (1 month) after the primary, the antibody production by the spleen lasted longer and higher serum titers were obtained. The bone marrow formed antibody in both cases but, particularly with the short interval between injections, its response was delayed as compared to the spleen. It was also shown that during antibody formation the production of gamma globulin in vitro was enhanced. Histologically the antibody production was always correlated to immature plasma cell proliferation, located at the border of red and white pulp and in the red pulp of the spleen. When endotoxin had been injected at the time of a primary BGG injection, and a second antigen injection was given 5 to 10 days later, a booster response could be elicited which was sometimes limited to the white pulp on day 1, and on day 2 was divided between "red" and "white" pulp. The response induced at day 10, at the peak of secondary nodule proliferation, lasted very long and was accompanied by an enormous plasma cellular proliferation in and around the periarteriolar lymphoid areas of the spleen. The possible importance of the secondary nodules of the white pulp in the preparation for a secondary response is discussed.