One of the most compelling problems concerning the immunobiology of lymphocyte populations is a better understanding of their unique capacity to migrate between the various fluid and tissue compartments of the body. Subpopulations of normal lymphocytes demonstrate distinct areas of localization for thymus-derived (T) and bone marrow-derived (B) cells in peripheral lymphoid organs. The factors which regulate recirculation of antigen-primed (memory) lymphocytes in general, and of B memory cells in particular, are less clear. Experiments will be undertaken, in mice, to further elucidate the effects of antigen deposition on the localization of specific antigen-primed lymphocytes. Experiments will be designed, using hapten-carrier conjugates, to analyze the specific localization of B memory cells in follicular areas within lymphoid tissues. Passive systemic immunization with homologous keyhole limpet hemocyanin (KLH) antibody followed by local injection of trinitrophenylated (TNP)-KLH in the left front footpad and the non-cross-reacting hapten, paraazobenzoate (PAB)-KLH in the right front footpad of irradiated recipients provides a suitable environment in the draining axillary and brachial lymph nodes to determine the effect of specific antigen-antibody complex deposition on localization of adoptively transferred, TNP-immune, B memory cells. Preliminary results indicate that TNP-immune B cells injected into such recipients will localize in the left lymph nodes draining the site of specfic antigen injection. Functional localization of B memory cells (i.e., their activation into TNP-specific antibody forming cells) will be demonstrated by systemic injection of carrier (KLH)-primed T cells and local challenge in both footpads with TNP- KLH. In addition to an investigation of the effects of antigen deposition within lymphoid tissues on localization of memory B cells, this approach offers a unique opportunity to investigate the influence of helper and/or suppressor T cells on memory B cell localization. Moreover, this model offers an excellent opportunity to assess the role of histocompatibility, I-region coded (Ia) antigens on lymphocyte recirculation and localization.