GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO* III. INDUCTION OF SECONDARY RESPONSE AT DI~lmRENT INTERVALS AFI'ER THE PRIMARY; THE ROLE OF SECONDARY NODULES IN THE PREPARATION ~FOR THE SECONDARY RESPONSE

It was shown previously (1) that the peak of antibody production in the spleen during the primary response to bovine gamma globulin (BGG) coincides with immature plasma cell proliferation at the border of red and white pulp. The so called "secondary nodules" in the white pulp reach their peak of development after the production of antibodies has subsided. Since the foUieular centers are therefore not major sites of antibody production during the primary response, the possibility that they may play another role in the immune process (2) such as preparing for the secondary response, a suggestion also made by White (3), has been investigated in the present study. This has been attempted by studying the secondary response induced at various intervals after a primary injection of BGG. It was felt that reinjection of BGG at the time of secondary nodule proliferation might produce a pattern of response different from that seen in the secondary response induced at 1 month after the first antigen injection. This study involves the preparation of roller tube cultures of spleen and bone marrow for the determination of antibody and gamma globulin synthesis, serum antibody titrations, and histological examination of the tissues at various days after the second intravenous antigen injection. It will be shown that the time of appearance of antibody production in the spleen during the secondary response, induced at 10 days after a primary injection of antigen, is quite different from that of the primary response, and also differs from that of the secondary response induced at 1 month after the primary. The findings suggest that the secondary nodules which are proliferating at the time of reinjection