The regulation of plasma cell function through soluble mediators of the CD28/B7 pathway

Abstract CD28 is the secondary co-stimulatory molecule that is crucial for optimal activation of naïve T cells and their differentiation into effector T cells. Activation of T cells without co-stimulation, renders the cells anergic. The influence of CD28 is not limited solely to T cells. CD28 as well as its ligand B7.1/2 are found on short- and long-lived plasma cells. We have demonstrated that signaling via CD28 acts as a negative regulator of plasma cell function. The removal of the CD28 signal leads to a hyperactive plasma cell state, with enhanced longevity, and increased antibody production in individual plasma cells. Interestingly, soluble forms of CD28, B7 and CTLA-4, are seen in the sera of patients with chronic human diseases, including autoimmunity, allergic asthma, and chronic hepatitis. We hypothesize that soluble CD28/B7 mediators will transiently block the CD28/B7 interaction on plasma cells and enhance autoantibody production. The research presented will compare the appearance and time course of the soluble mediators in mouse models of chronic and acute disease.