AGE-ASSOCIATED MODULATION OF APOPTOSIS AND ACTIVATION IN MURINE B-LYMPHOCYTES

We have investigated the influence of age on B-cell responsiveness. Th e present study showed that the B-cell mitogen, lipopolysaccharide (LP S), similarly stimulated the proliferation of purified B lymphocytes o btained from either young mice (3 months) or old mice (24 months). In contrast, expression of the differentiation marker, alkaline phosphata se (ALP), was about fourfold higher in young mice than in older mice u pon stimulation with LPS or with dextran sulfate (DXS) and interleukin -5 (IL-5). The occurrence of apoptosis during aging was then studied: unexpectedly, spontaneous cell death was double in B lymphocytes from young mice compared to older animals. Stimulation with DXS with or wit hout IL-5 rescued B lymphocytes from cell death in young mice but prot ection decreased with aging, and no longer occurred in 24-month-old mi ce B cells. Meanwhile, the protective activity conferred by IL-4 was m aintained at similar levels throughout aging. However, B cells from ol d mice were more responsive to apoptosis induction with cycloheximide, dibutyryl cAMP and dexamethasone. Together, the present results indic ate an age-associated alteration in apoptosis and activation of B lymp hocytes which could contribute to the age-related decline of the immun e response. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved .