Here are more indications that selective pruning of an aged immune system can restore at least some of its youthful potency. If researchers can understand why the pruning does this, then there is the possibility of skipping the selective destruction and directly manipulating the underlying signaling processes instead: "Age-related alterations in the cellular composition of the B lineage are a major cause of the poor antibody response to vaccination and to infectious agents among the elderly population. The mechanisms leading to these changes are poorly understood. Recently, we have shown that these changes reflect, at least in part, homeostatic pressures imposed by long-lived B cells that accumulate with aging, and that aging in the B lineage can be reversed upon alteration of B cell homeostasis by depletion. Here we discuss homeostatic causes for B lineage immunosenescence, and the potential for its rejuvenation. ... The major conclusion of our study is that age-related alterations in the B lineage are reversible and mediated [by] the long-lived B cells accumulating in the periphery with age ... These observations are the foundations of new paradigms for enhancing immune responsiveness in aging, which may be translated in the future for clinical use. The nature of these homeostatic regulation mechanisms and the cross-talk between peripheral B cells and progenitor cell populations in the [bone marrow] are yet to be identified. This will allow direct manipulation of B cell homeostasis by targeting the regulatory factor(s) rather than by depletion of B cells, to [enhance] immune competence in the elderly."