Antibody responses to antigenic determinants of influenza virus hemagglutinin. II. Original antigenic sin: a bone marrow-derived lymphocyte memory phenomenon modulated by thymus-derived lymphocytes.

Mice immunized sequentially with two related influenza virus hemagglutinins (HA) produced a secondary antibody response with two different specificities. Some antibodies were specific for determinants common to both HA's. Paradoxically, some antibodies were directed to determinants existing only in the HA first encountered. Primed spleen cells treated with anti-theta serum and complement were transferred from animals immunized with the first HA to either normal, irradiated, or thymus-deprived recipients. These memory cells were boosted in the recipients with either the homologous or the heterologous cross-reacting HA. B-memory lymphocytes were shown to be directly triggered by both HA's and to be able to secrete, independently of T lymphocytes, antibodies to both kinds of determinants. However, T cells were shown to modulate this secondary response by either enhancing or suppressing antibody secretion by B-memory cells, depending on experimental conditions. These results are discussed in terms of antigen recognition by B cells and of kinetics of development of immunological memory.