This renewal will continue studies of the ligand-induced factors that affect the formation of the responsive B-cell repertoire. Studies to date have demonstrated a heritable pattern of turnover in the emerging B-cell pool, which perturbed by ligand exposure. These induced perturbations are long-lasting, and result in oligoclonal profiles due to the generation of reglatory cell subsets, as well as changes in the stimulated B-cells themselves. This proposal will examine these induced regulatory cell populations, as well as the precise nature of changes which occur among the B-cells themselvs, as a result of neonatal priming. The helper requirements and specificity for primary versus secondary B-cells will be assessed by limiting dilution analysis of Th cells. The specificity, genetics, and mechanism of action of neonatally induced suppressors will be assessed by genetic studies using recombinant congenics, stimulation with various hapten-HA combinations, and examination of cell surface markers on the induced suppressors. Finally, the half-life properties of primary vs secondary B-cells will be examined through in vivo and adoptive transfer labeling studies.
