Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/naïve B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro-and anti-inflammatory cytokines, tumor necrosis factor (TNF)-a and interleukin (IL)-10, and presence of somatic hypermutation, focusing on the IgG ? IgD -CD27 -double negative (DN) B cells that are expanded in the elderly. Our results show that naïve B cells from young donors need a sufficiently strong stimulus to be activated ''in vitro'', while naïve B cells from old subjects are able to produce IL-10 and TNF-a when stimulated ''physiologically'' (a-CD40/IL-4), suggesting that these cells might play a role in the control of the immuno-inflammatory environment in the elderly. In addition, in the elderly there is an accumulation of DN B cells with a reduced rate of somatic hypermutation. Thus, DN B lymphocytes may be exhausted cells that are expanded and accumulate as a by-product of persistent stimulation or impaired germinal center formation.