B cells and aging: gauging the interplay of generative, selective, and homeostatic events

Lymphocyte homeostasis encompasses a continuum of processes that together determine the production, turnover, composition, and representation of lymphocyte pools. These processes include commitment to lymphoid lineages, expansion of progenitor pools, successful transit through intermediate maturation stages, negative and positive selection based on receptor specificity, steady-state maintenance of peripheral lymphocytes, and regulation of antigen-driven activation. Understanding the impact of aging on lymphocyte homeostasis thus requires appreciation of not only the mechanisms responsible for generating and sustaining antigen-reactive B and T cells but also how age-related events can subvert these. Even under the influence of normally operating homeostatic mechanisms, lesions yielding perturbations outside of evolutionarily anticipated boundaries will yield aberrant lymphoid function and representation both upstream and downstream of the primary defect. Accordingly, determining the relative contribution of lineage-intrinsic versus compensatory homoeostatic processes throughout the continuum of lymphoid system development, selection, and maintenance are critical first steps towards understanding age-associated alterations in the immune system.