In addition to their established role as cytotoxic effector cells, previous studies proposed that NK cells may regulate B cell responses to antigens. Both enhancement and suppression of Ig synthesis by NK cells have been reported. Our previous studies have also demonstrated that NK augmentation is mediated on both IgG and IgM responses. NK cells are a subpopulation of lymphocytes characterized primarily by their cytolytic activity. They are recognized as an important component of the immune response against virus infection and tumors. In addition to their cytolytic activity, NK cells also participate either directly or indirectly in the regulation of adaptive responses, i.e. the initiation of an Ab response. More recently, our studies have demonstrated that human NK cells can induce autologous resting B cells to synthesize Ig, including switching to IgG and IgA, reminiscent of a secondary Ab response. Translating these finding into a murine model has both reproduced these findings and extended them into a primary immunization model utilizing TNP-KLH as an antigen. Our results indicate that NK cells can significantly alter the quality and quantity of anti-TNP antibody in vivo. Mechanistically, the removal of NK cells prior to immunization results in significant increases in antigen specific T and B cells in the host. Much of this regulation of Ig production appears to be through the regulated production of soluble factors in the host immune organs. The existence of this novel mechanism of B cell regulation has important implications in innate immunity, B cell-mediated autoimmunity, and B cell neoplasiaInnate immune responses provide the body with its first line of defense against infections. Signals generated by a subset of lymphocytes, including natural killer (NK) cells, natural killer T (NKT) cells, and antigen-presenting cells during the early host response determine the nature of downstream adaptive immune responses. A recent study in autoimmune models has implied early regulation of the adaptive interface. In the present study, we have extended these observations to MOG peptide induced EAE. Our studies have shown that NK cells can affect the outcome of these adaptive immune responses as NK cells, but not NK1.1+T cells, were found to regulate the degree of clinical and immune adaptive responses to MOG (35-55). The requirement for NK cells was reflected by the alteration of helper T cell response, dendritic cell maturation and clinical disease was seen in mice treated with anti- NK1.1, anti- asGM1, and selected Ly49 subtype-depleted mice. These findings establish a previously unexplored link between NK cells and autoreactive T and B cells as well as establishing an important role for NK cells in the initiation and amplification of adaptive responses.
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