GENERATION OF B CELL MEMORY WITH AGING

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Humoral immunity decreases with aging and contributes to the increased incidence and accompanying morbidity and mortality of infections and to the poor immunogenicity of vaccines in this age group. Although there are multiple etiologies of the decreased humoral immunity with aging, intrinsic defects of aged B lymphocytes and their precursors may make an important contribution to defective primary antibody responses, the low affinity antibody response, and poor persistence of memory. We hypothesize that contributing to these defects in aged humans are the poor generation of memory B cells that is associated with limited diversification of antibody responses and low levels of somatic hyper mutation of immunoglobulin(lg)variable (V) region genes and the poor persistence of memory B cells secondary to shortened telomere length that limits their longevity. We have recently developed an approach to activate and recover a diversified human antibody repertoire after immunization that can be analyzed at the molecular level and methods to up regulate expression of telomerase in memory B cells. Using these approaches, we propose to determine whether immunized healthy elderly adults generate diversified antibody repertoire with somatic hyper mutation and memory B cells to the same extent as young adults and to investigate whether telomerase is up-regulatable in- vitro and telomere shortening occurs in-vivo in B lymphocytes of elderly adults. The results should provide insight into the poor humoral immunity that occurs with aging and a background for developing interventions to reverse immunosenescence or improve, vaccines for the elderly.