The rapid expansion of the aged population, the increased incidence of gastrointestinal infections ad diseases and the age-related decline in immunocompetence demonstrate the need for a comprehensive, quantitative analysis of the mucosal immune system as a function of age. Furthermore, recent evidence from our laboratory suggest that the suspected age-dependent decline in the levels of immunoglobulins in the gut lumen may reflect, in part, a concomitant decline in the levels of hepatobiliary secreted immunoglobulin A (IgA). While current dogma states that aging affects the cell-mediated immune response more markedly than the humoral response, there are data which suggest that intrinsic alterations in B-lymphocyte or non-lymphoid elements may also play a role in this immunodeficiency. The relationship between apparently independent parameters, e.g. age, decline in the immune response and hepatobiliary secretion of IgA and the increased incidence of gastrointestinal infectious diseases, may be more than coincidental. We propose to elucidate the cellular site(s) and/or mechanisms responsible for possible age-related changes in the secretion of IgA by hepatocytes of the rat. In order to achieve this objective, we propose to examine several specific properties and functions of the IgA receptor as a function of age, including: (1) the binding properties of the IgA receptor in isolated hepatocyte plasma membranes; (2) the binding and endocytosis of IgA by isolated hepatocytes from animals of various ages; (3) the transport of IgA bound to its receptor through the hepatocyte and (4) the effect of age on the turnover and synthesis of the IgA receptor. The summation of this combined structural and functional approach will be an excellent index of the effect of age on the properties and function of the IgA receptor.
