Immunity to infectious microorganisms is dependent on the successful integration of humoral and cellular immunity. T helper cells are known to modulate both types of immune responses by producing polarized arrays of immuno-regulatory type-1 and type-2 cytokines which activate macrophages to kill pathogens and help direct B cells to produce protective antibody. Recently, we demonstrated that B cells, like T cells, can be induced to differentiate into effector subsets that produce distinct arrays of cytokines. We also showed that these effector B cells (Be-1 and Be-2) present antigen to naive T cells, and produce polarizing cytokines such as IFN-g, IL-12 and IL-4, thus inducing the differentiation of T cells to fully functional polarized Th1 and Th2 effectors. Importantly. cytokine-producing Be-1 and Be-2 cells were identified in animals infected with pathogens that preferentially induce polarized type-1 or type-2 immune responses. Thus, B cells can potentially contribute in multiple ways to immune responses, by producing protective antibody as well as by making regulatory cytokines. Interestingly, it has been recently demonstrated that B cells actively regulate the magnitude of the T cell response and type of T cell immunity generated, particularly in response to infectious agents. Although it is not known how B cells regulate immune responses, it has been shown to be independent of antibody production. Based on our results, we postulate that one mechanism by which B cells modulate cellular and humoral responses to infectious pathogens is through production of discreet arrays of cytokines which can direct the activities of other immunocytes, such as T cells. To test this hypothesis, we will first examine whether cytokine production by B cells regulates humoral immune responses at either the B or T cell level. Next, we will characterize the signals that induce effector B cell development. Finally, we will test whether cytokine-producing effector B cell populations are required for immune protection in a model of infectious disease. Together, these experiments will determine how cytokine production by B cells influences humoral and cell-mediated immunity. Additionally, the experiments will help to elucidate the multiple """"""""effector"""""""" roles of B cells in immune responses to infectious microorganisms, potentially facilitating the design of vaccines that better target all of the protective effector functions of B cells.
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