Proliferative responses of B cells from elderly humans: abnormalities in early responsiveness are related to...

Age-related changes are known to occur in the function of human T cells but less information is available about human B cells during aging. In this study, B cells obtained by negative selection from the peripheral blood of young and elderly subjects were stimulated in vitro with anti-IgM, Staphylococcus aureus Cowan strain I (SAC), or Staph protein A (SpA) from SAC. Their proliferative capabilities with and without lymphokines were quantitated by [3H]thymidine uptake. Stimulated B cells from elderly subjects were reduced in their overall ability to sustain normal levels of proliferation observed for B cells from young subjects. However, time course studies analyzing early proliferative responses revealed that B cells from one subset of elderly displayed persistent hyporesponsiveness whereas another subset demonstrated early hyperresponsiveness compared to B cells from young adults. Experiments to determine the frequencies of B cells with transferrin receptors (TfR) and low-affinity receptors for IgE (Fc epsilon RII/CD23) showed reductions in the expression of these two glycoproteins among stimulated B cells from elderly with the persistent decreases in proliferation. By contrast, unstimulated B cells of elderly subjects with early hyperresponsiveness displayed increased frequencies of TfR-positive cells, which became reduced after stimulation. Further, stimulated B cells from this group demonstrated greater frequencies of CD23 positive cells than young adults (13 vs. 8%). Thus two distinct profiles of proliferative abnormalities can be observed in early cohorts of activated B cells from elderly humans. The association of these abnormalities with differences in TfR and CD23 suggests that certain age-related defects occur relatively early during the B cell activation scheme.