Determinants of the hierarchy of humoral immune responsiveness during ontogeny.

A model system of ontogeny was utilized to investigate the development of humoral immunity in both AKR and BALB/c mice. Lethally irradiated adult mice were reconstituted with syngeneic fetal or neonatal liver. These mice were immunized at various times after reconstitution with a series of eight antigens: the bacteriophages F2, phiX-174, and T4; the hapten carrier complexes 2,4 dinitrophenyl-bovine serum albumin and fluorescein-bovine serum albumin; and the small proteins: hen egg lysozyme, sperm whale myoglobin, and bovine pancreatic ribonuclease. Subsequent antibody production to the antigens was assayed with either a direct or a modified bacteriophage neutralization technique. Individual mice responded to the various antigens in a sequential pattern which was basically the same for all mice within each strain. However, there was a marked difference between the two strains in the time at which they developed responsiveness to myoglobin. In order to begin to delineate the separate roles played by B and T cells in the generation of this hierarchical response pattern during ontogeny, the development of anti-DNP and anti-FTC activity was examined in carrier-primed mice. Results of this experiment indicated that functional B cell specificities for the two haptens arise at different times during ontogeny. Further studies are needed to determine whether the hierarchical pattern of immune responsiveness observed for the other antigens is a function of sequential appearance of B cell specificities, T cell specificities, or both.