The murine CD21/Cr2 gene encodes two proteins implicated in the acquisition of an optimal immune response. The CD21 pathway includes signals for B cell survival and optimal activation, and presentation of native antigen by follicular dendritic cells (FDC) in the germinal centers of the spleen. The expression of murine CD21 is tightly controlled. The proteins are found on B cells during specific stages of differentiation and are expressed by FDC once they have taken up their position within the spleen. This competing application proposes to continue our analysis of the mechanism of CD21 gene control and the functions of the CD21 proteins in the generation of an appropriate immune response. We have demonstrated that promoter and intronic elements regulate the CD21 gene. We propose to continue our analysis of the transcriptional control of CD21, incorporating the comparative analysis of two other genes, CD19 and CD23, that are expressed at similar times of B cell differentiation. We will also continue our examination of a mutant mouse line with an engineered deletion of the CD21 intronic control region. These analyses also include the role of transcriptional activators from herpes virus that induce CD21 and CD23 expression, and the effect of such over expression on the immune response. Our analysis of the function of the CD21 proteins will focus upon the role of the CD21 proteins as complement receptors enhancing both the acquired and innate immune responses including the generation of the immunoglobulin isotypes. We will also analyze the role of various gene products whose expression is critically altered in CD21 deficient animals during immune activation. The generation of an appropriate immune response is critical to the health of the individual. The CD21 proteins straddle the fields of acquired and innate immune responses such that their manipulation could influence immediate responses to an infection as well as the more long term consequences of immunologic memory.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Innate Immunity and Inflammation Study Section (III)
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Davidson, Wendy F
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University of Utah
Schools of Medicine
Salt Lake City
United States
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Donius, Luke R; Orlando, Christopher M; Weis, Janis J et al. (2014) Generation of a novel Cr2 gene allele by homologous recombination that abrogates production of Cr2 but is sufficient for expression of Cr1. Immunobiology 219:53-63
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Lochhead, Robert B; Sonderegger, F Lynn; Ma, Ying et al. (2012) Endothelial cells and fibroblasts amplify the arthritogenic type I IFN response in murine Lyme disease and are major sources of chemokines in Borrelia burgdorferi-infected joint tissue. J Immunol 189:2488-501

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