Dysregulation of B cell homeostasis in aged mice

Schmidt, Madelyn

Abstract

New lymphocytes must constantly replenish the long-lived mature lymphocyte to maximize immune repertoire diversity and responsiveness. As individuals age there is a generalized diminution of immune function, immunosenescence, which progressively restricts responses to new antigenic challenges; preventing efficient vaccination of the elderly and increasing their susceptibility to infection. One proposed mechanism of immunosenescence is that aging diminishes lymphopoiesis in the primary lymphoid organs reducing the production of naive B and T cells. We have used an adoptive transfer model to determine the replicative potential of naive B cells in the absence of antigen exposure. We find replication of naive B cells is greatest in B ell deficient recipients but 6that replication was significantly reduced in aged recipients despite their being B cell deficient. These preliminary results were used to formulate a more competitive view of immunosenescence: we hypothesize that newly produced naive B cells are restricted from entering the pool of long-lived B cells by changes in the aged microenvironment. Because naive B cells are the major responders to new antigens, the inhibition of their entry reduces the diversity of the immune repertoire and immune responsiveness. The goals of this pilot project are to assess preliminary the mechanistic basis for age dependent homeostatic dysregulation. We will: (1) determine if B cell homing to or localization within the spleen is affected by aging or is due to other changes in the aged microenvironment, (2) if quantitative or qualitative changes in aged B cells are inhibitory, and (3) establish if aged T cells inhibit naive B cell entry and/or expansion.