The role of MerTK and BAFF in dendritic cell-B cell interactions Public Deposited

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  • March 22, 2019
  • Gohlke, Paul Reid
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Autoimmune disease occurs when the system of cells and molecules designed to protect the host from invading pathogens directs itself towards attacking the host. The development of autoimmunity involves the participation of several cell types each with a distinct role in disease pathogenesis. Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which autoreactive B cells produce antibodies directed against ubiquitous components of the cell nucleus. Although B cells are the effector cell type in this process, specific genetic deletions in mouse models have shown that improper function of the non-B cell components of the immune system can be sufficient to coerce otherwise tolerant B cells into becoming autoantibody-producing cells. Mice lacking a functional version of the receptor tyrosine kinase MerTK (mertkkd mice) are one such model. As in SLE, mertkkd mice develop autoantibodies to antigens normally found in the cell nucleus such as dsDNA, ssDNA, chromatin, and Sm. While MerTK is not normally expressed by B or T cells, it is expressed by myeloid-lineage cells such as dendritic cells and macrophage. Since dendritic cells are known to both, present antigen to B cells, as well as produce the cytokine BAFF, we decided to investigate the possibility that dendritic cells from mertkkd mice are facilitators of B cell autoimmunity. Our experiments demonstrate that MerTK functions to restrict spontaneous BAFF production by dendritic cells. However we have also determined that dendritic cells have a pro-survival effect on B cells that is independent of both MerTK and BAFF. In an effort to further our understanding of the importance of dendritic cell-derived BAFF in vivo we have also generated a targeting construct, DT-BAFFflox, that will permit conditional deletion of the baff gene in dendritic cells. Future application of DT-BAFFflox towards creating a baffflox mouse, in conjunction with the proper Cre transgenic mouse, will highlight the role that dendritic cell-derived BAFF plays in mertkkd mice and other models of autoimmunity.
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  • Matsushima, Glenn
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  • University of North Carolina at Chapel Hill
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