Age-dependent changes of B-cell reactivity and T cell-T cell interaction in the in vitro antibody response☆

Abstract The in vitro anti-2,4,6-trinitrophenyl (TNP) antibody response of spleen cells from 1- to 32-month-old mice was evaluated by techniques suitable for dissecting out T- and B-cell reactivities. Spleen cells from individual mice carrier primed with horse red blood cells (HRBC) were immunized in vitro with TNP-HRBC, a T-dependent immunogen. The anti-TNP antibody response was found to change with the increasing age at which the animals were carrier primed, so that the response at 24 months was only about 4% of that at 3 months of age. It was also found that the variability in response among mice of the same age increased exponentially with age, suggesting that during senescence the immune system is impaired by stochastic events. A substantial part of the decline in immune responsiveness reflects the age-dependent decrease of B-cell reactivity as shown by marked reduction of the anti-TNP antibody response of spleen cells from old mice upon in vitro immunization with TNP-Ficoll, a T-independent immunogen. To analyze helper T-cell activity of aging mice independently from age-associated changes in B-cell reactivity the helper cell function was titrated by adding graded numbers of HRBC-primed spleen cells from individual mice of a given age to cultures containing a constant number of normal spleen cells from a pool of 3-month-old mice and the immunogen TNP-HRBC. The anti-TNP antibody response increases with the number of primed cells added to culture and the log number of anti-TNP plaque-forming cells is a linear function of the log number of the primed cells added. This linear regression was used to evaluate T cell-T cell interactions. This analysis unmasked in aging mice a decrease in the ability of T cells to interact synergistically in the generation of helper activity.