The control of antibody production by immunomodulatory molecules

Regulation of human B cell responses is a complex process that involves the activities of a variety of cytokines. There are important differences between the regulation of human and murine B lymphocytes, especially with regard to the action of IL-2. In humans, IL-2 appears to play a central role in regulating B cell activation, proliferation, and differentiation, thereby facilitating the production of immunoglobulins of all isotypes. A wide array of additional cytokines can amplify antibody production, but none appears to be able to do this in the absence of IL-2; moreover, none appears to enhance the production of only a single isotype of immunoglobulin. Beyond the positive influences of cytokines on B cell responses, at least 2 cytokines, IL-4 and TGF beta, suppress B cell proliferation and differentiation. Inhibition by each of these cytokines can be overcome by specific cytokines that provide positive signals to B cells. Antibody production is thus regulated by a complex array of cytokines with complementary or opposing effects that may be exerted at different stages of B cell responsiveness. Whether specific subpopulations of B cells exhibit unique cytokine requirements for differentiation has not been clearly delineated, nor is it clear whether autoantibody production is uniquely regulated by cytokines. Additional information concerning the role of cytokines in the regulation of B cell function should provide further insight not only into normal antibody production, but also into potential dysregulation that leads to autoimmunity.