Reduction in the Quantity of the Polymeric Immunoglobulin Receptor Is Sufficient to Account for the Low Concentration of Intestinal Secretory Immunoglobulin A in a Weanling Mouse Model of Wasting Protein-Energy Malnutrition

The main objective of this investigation was to determine the influence of protein-energy malnutrition (PEM) in weanling mice on the expression of the hepatic and intestinal polymeric immunoglobulin receptor (pigR), a molecule that transports mucosal immunoglobulin A (IgA) into the intestinal lumen. An experimental system was used that produces systemic wasting (loss of approximately 1.9% of initial body weight per day) and that exhibits fidelity to human PEM in its influence on the concentration of IgA in critical biological fluids as well as in its influence on lymphoid involution and thymus-dependent immunocompetence. Male C57BL/6J mice were allocated to a zero-time control group (19 d of age) or to groups fed for 14 d as follows: free access to a complete purified diet (19% crude protein, 17 kJ/g gross energy) or free access to a low protein diet (0.5% crude protein). The concentration and total quantity per organ of the pIgR were assessed in the liver and intestine by Western immunoblotting using an antiserum raised against the secretory component portion of rat pIgR. Malnourished mice exhibited low quantities of hepatic and intestinal pIgR relative to well-nourished controls (0.4% and 36% of control, respectively) and also exhibited a low concentration (soluble-protein basis) of hepatic pIgR (2% of control). The concentration of biliary secretory component also was low in the malnourished mice (4% of the value for well-nourished controls). Finally, Western blotting revealed an eightfold increase in serum concentration of dimeric IgA in the malnourished group relative to well-nourished mice, whereas the levels of the monomeric form and of the higher order polymers of IgA were elevated by factors of three and two, respectively. In this experimental system, decreased expression of the pIgR is sufficient to account for the low concentration of IgA that is maintained in the mucous secretions of the intestine.