This project will examine aspects of the heritable and inducible mechanisms involved in the formation of an antibody repertoire. First, limiting dilution systems will be used to analyze the qualitative and quantitative requirements of primary and secondary influenza hemagglutinin (HA) specific B lymphocytes for T lymphocyte help. Second, various inbred, recombinant inbred, and congenic strains of mice will be used to determine the position and number of loci on chromosome 12 that mediate the effective interactions of helper T lymphocytes (Th) and neonatally induced suppressor T lymphocytes (Ts). Third, in vivo labeling of unprimed and primed B lymphocytes will be done to assess the role of antigen-induced alterations of B lymphocyte lifespan. Finally, a library of HA-specific hybridomas will be constructed and screened for immunoglobulin V-region structural gene usage, to determine the mechanisms responsible for the heritable patterns of antibody repertoire expression. These studies will extend our knowledge of the oncogenesis of the antibody repertoire and may provide insight relevant to the efficiency and potential hazards of neonatal immunization (either environmental or by vaccination).
