Immune function in aged mice. II. B-cell function.

A loss of B-cell function in old mice was demonstrated by measuring the in vitro response of lymphoid cells to the B-cell polyclonal activator, LPS (lipopolysaccharide), and the in vivo response to the thymus-independent antigen, pneumococcal polysaccharide type III (SIII). The reduced mitogenic reactivity of lymphoid cells from old compared with young mice could not be explained by a shift in kinetics of the responding cells. When LPS cultures were carried out in the presence of colchicine, fewer cells from old mice were found to respond to the mitogenic signal. The total number of B cells assessed by labelling with either anti-immunoglobulin serum or antigen-antibody complexes was not decreased in old animals. Taken together, these results are consistent with a qualitative rather than a quantitative loss of B-cell function with age. They did not, however, exclude the possibility of depletion of an LPS-reactive sub-population of B cells. Since the number of LPS-reactive cells could not be determined directly, the antibody response of old mice to SIII was investigated. The decreased level of antibody production by old mice to SIII was not due to a shift in kinetics of the responding cells. Extracellular influences were excluded by showing that the reduced responsiveness of old spleen cells persisted after adoptive transfer into young irradiated recipients. Furthermore, pretreatment of cells from old mice with anti-Thy.1 serum and complement before transfer did not enhance their antibody-forming potential. The loss of B-cell activity with age could not, therefore, be explained in terms of an increase in T-cell-dependent suppressive effects. Support for an intrinsic defect in the B cell itself came from the demonstration of similar numbers of SIII-binding cells in normal spleens from old and young mice. Following immunisation, a shift toward low intensity binding cells was observed in spleens from both old and young mice. This shift was, however, less pronounced in the case of old cells, which is consistent with an age-related decline in transformation potential of antibody-forming-cell precursors. The conclusion was, therefore, reached that the reduction with age in B-cell as well as T-cell function is due to a qualitative rather than a quantitative defect in lymphocytes themselves.