The experiments outlined in this proposal examine the longevity and nature of effects induced by neonatal immunization upon the phenotypically expressed antibody repertoire. Whether ligand-induced effects are long-lived following either acute or chronic exposure will be assessed by defining the influenza hemagglutinin (HA) specific repertoires of adult BALB/c mice which have received such treatments. Whether these effects are predictable will be determined by similar analyses of animals whose initial exposure to antigen was at different ages. The mechanisms of these effects will be studied (i) by determining whether specific T-cell subsets contribute to the skewing of adult phenotype and (ii) whether the HA-responsive B-cell population changes in differentiation state as assessed by serologic and functional criteria. In addition, the possibility that these predictable, induced effects provide a general mechanistic model for the phenomena of clonal dominance and """"""""original antigenic sin"""""""" will be investigated. Finally, hybridoma libraries representative of neonatal clonotypes will be generated from the spleens of chronically immunized adult mice.
