This Program Project brings together three laboratories with a common interest in understanding the normal mechanisms of B and T cell development, maintenance and memory generation and aging associated alterations in these processes. Dr. Klinman's Project will continue to analyze alterations in B cell development in aged mice with respect to pre B cell clonal maturation and expansion, receptor mediated selection, and the generation and propagation of somatically mutated memory B cells. Projects represent new initiatives for the study of the basis of altered T cell responsiveness in aged mice. In Project by Dr. Linton will investigate the effects of aging on T cell subsets in four lines of TcR transgenic mice. These studies will incorporate an already successful collaboration with Dr. Susan Swain and important new collaborations with Drs. Linda Sherman and Dr. Jonathan Sprent. In Project by Dr. Sprent will attempt to further our understanding of T cell turnover in young and aged mice and assess the impact of cytokines on the generation and maintenance of memory T cells. The research proposed in this Program Project not only brings together the efforts of several leading T and B cell immunologists, but also represents a series of highly advantageous collaborative interactions. In Project by Klinman, Dr. Sprent will participate in the analysis of cell division in developing B cell subsets and Dr. Linton will collaborate in the investigation of the in vitro generation of memory B cells. In Projects by Drs. Linton and Sprent will jointly investigate the role of antigens and cytokines in the maintenance of the memory T cells in aged mice. The combined expertise and concerted efforts of these accomplished investigators, with the support of a Core that provides first rate FACS and common animal maintenance facilities, should enable significant progress in determining the basis for the aging associated alterations in immune responsiveness.