Age-related alterations in the activation and expression of phosphotyrosine kinases and protein kinase C (PKC) among human B cells

Abstract

Age-related changes in the functional properties of human B cells have been reported by several groups, but little is known about the early biochemical events and signaling pathways that might be altered during aging. The present investigation examined whether differences in the activation of protein tyrosine kinases (PTK) and in the expression of protein kinase C (PKC) enzymatic activity could be identified in B cells from 16 elderly subjects (mean 77 years) compared to B cells from 15 young subjects (mean 33 years). B cells from young subjects stimulated with the surface immunoglobulin (sIg) crosslinkers anti-IgM or Staphylococcus aureus Cowan I (SAC) demonstrated rapid increases in PTK mediated de novo tyrosine phosphorylation of endogenous proteins. In comparison, stimulated B cells from elderly subjects were reduced 22–46% in tyrosine phosphorylations. Quantitation of the enzymatic levels and activation/translocation of PKC activity among resting and sIg stimulated B cells showed that B cells from ∼ 50% of elderly subjects had significant reductions compared to B cells from young subjects. Further analyses of the expression of PTK and PKC enzymatic activity by stimulated B cells from elderly subjects demonstrated that aging was associated with greater heterogeneity in PKC expression and that defects in PKC enzymatic activity could coexist with relatively normal PTK activity. Thus, these data suggest that aging can alter the expression of PTK/PKC enzymatic activity in human B cells and that these age-related alterations might perturb the balance between PKC-dependent and -independent signaling pathways.