Vocal Voices

there is another matter of historical interest associated with the results described in this volume. The scientists who proposed the elements of the clonal selection theory in the 1950s thought that the immune response would be driven entirely by antigen and that, when antigen disappeared, the immune response would cease (1-3). These scientists also expected that the primary immune response would create relatively small numbers of antigen-specific cells, cells that would survive more or less in toto, to become memory cells, when the primary infection was over. Now we know that the clonal selection theory was wrong on both these fronts. In spite of the fact that this theory accurately predicted many aspects of the immune response, it fell short in its predictions about the end of immunity, as amply demonstrated by the articles herein. For example, we now know that immune responses are accompanied by tremendous increases in the numbers of antigen-specific T cells (4-9) and to a lesser extent B cells (10). Clearly, most of these cells must be destroyed to make space, cytokines, and nutrients available for other cells and also to avoid huge amounts of inflammation were all these cells to be reactivated. Thus, biology has arranged that most of the antigen-specific cells generated during an infection disappear. The processes that control such removal are discussed at length in several articles in this volume (11-18). Nevertheless, not all antigen-induced cells die, many survive to create the memory cells (predicted by the clonal selection theorists) that protect us against reinfections (16, 19, 20).