B-cell intrinsic Type 1 and Type 2 interferon signaling in regulating spontaneous germinal centers and autoimmunity

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

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Abstract

? DESCRIPTION (provided by applicant): A healthy immune response to infection involves development of highly specific antibodies that recognize and mark invading pathogens to be safely cleared from the body. The pathogen-sensing portion of these antibodies can be modified to provide enhanced recognition of the pathogen resulting in improved immune response to that pathogen. These antibody-editing events occur in the dynamic structures called germinal centers that develop in the spleen and lymph nodes during an immune response. In autoimmune diseases like systemic lupus erythematous (SLE), poor regulation of the germinal center results in abnormal antibody editing that could cause antibodies to recognize the patient's own tissue rather than pathogens. These highly specific antibodies (referred to as autoantibodies) target healthy cells in the patient to result in progressive organ destruction and end-stage lupus disease. This study will focus on the regulation of the germinal center by interferon signals that are produced to control the immune response (including germinal center regulation). Here, we will specifically focus on characterizing the interferon-associated signals that alter germinal center regulation and cause the production of autoantibodies. Characterizing these events will build the foundation for the discovery of new targets for highly focused lupus treatments that improve the prognosis for patients suffering from this debilitating disease.