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Learning and Memory in the Immune Response¹

Department of Microbiology, Washington University School of Medicine, Saint Louis, Missouri

Following 1 injection of rabbits with moderate amounts of some dinitrophenylated proteins, the 7 S antibodies formed initially have low average affinity for the 2,4-dinitrophenyl (DNP) group, and appear relatively homogeneous with respect to affinity. The anti-DNP molecules formed later appear more heterogeneous in binding activity and have higher average affinity for the DNP group. The rate of increase in affinity, and of heterogeneity in binding activity, is retarded by large doses of the immunogen (> 100 mg/animal). After the response to the 1st injection has subsided, a 2nd injection of the immunogen evokes a burst of synthesis of anti-DNP molecules which, within a few days, have the same binding properties as those formed many months after the initial injection. The results are interpreted in terms of selective stimulation or repression of diverse anti-DNP-producing cells, with the level of immunogen controlling the cell's activity or dormancy by interaction with hypothetical "sentinel" antibody molecules on the cell's surface. In keeping with this interpretation, in the secondary response elicited by an immunogen that resembles the initial immunogen (e.g., TNP-protein for the 2nd and DNP-protein for the 1st injection), the antibodies formed were much like those that would have been formed to a 2nd injection of the original immunogen.

¹ Based on talks presented as the J. Howard Mueller Memorial Lecture at the Harvard Medical School, Boston, Mass., December 8, 1964, and as The Enrique Ecker Lecture at the Western Reserve University School of Medicine, May 1965. This work was supported in part by a USPHS research grant (AI-03231), and a training grant (5T1-A1-257), both from the National Institute for Allergy and Infectious Diseases, and by a contract with the Research and Development Command, Department of the Army, recommended by the Commission on Immunization of the Armed Forces Epidemiological Board (DA-49-193-MD-2330).