The principal goal of this proposal is to analyze the molecular and cellular events leading to the changes in antigen-specific antibody repertoire seen in the immune response of the aged. This will be accomplished using a murine experimental model of peripheral lymphoid auto-reconstitution by the bone marrow while the long bones are shielded. We will analyze the VH gene usage in the antibody response to a thymic-independent antigen and determine whether its expression in aging is a stochastic representation of the available repertoire or is a skewed antibody response. This information is crucial to the understanding of the acquisition of immunity to bacterial agents by the aged. We shall also study the role of T cells in the regulation of antibody repertoire expression. This will allow us to determine the role of T cells in the aging immune response. Anti-viral responses require collaboration between B and T cells. Such studies will point the way towards possible enhancement of the aged's responses to microbial agents. Finally, we shall determine the mechanisms leading to the apparent loss of high-affinity antibody by the aged. We shall compare immunological memory acquisition by the young and the aged. This will allow us to identify modalities under which high-affinity antibody producing B cells might be augmented in the immune response of the aged. Since it is generally recognized that high-affinity antibody is most effective in fighting-off infections, such data are essential to our knowledge of the physiology of the immune response of the aged.
