THE ROLE OF COMPLEMENT IN AUTOIMMUNITY

Summary

Principal Investigator: GARNETT H KELSOE
Abstract: To study the role of complement (C) and C receptors (CRs) in controlling B-cell development and the antibody repertoire, humoral immune responses, and spontaneous autoimmunity, we shall generate congenic lines of mice that are deficient for the classical and/or alternate C pathways and for specific combinations of CR ligands. These animals will be used to map genetically the separate and combined roles of Clq, C4, C3, and CR1 and -2 in selective clonal deletion, anergy, and secondary V(D)J rearrangement in developing B lymphocytes, germinal center and serum antibody responses, clearance of dead cells and cellular debris, and the promotion of autoimmunity. We propose that C and CR deficiencies promote self-reactivity by two distinct but mutually supportive pathways: alteration of central tolerance and the B-cell repertoire by the effects of CR1/2 and their ligands and impaired removal of immunogenic cellular debris and immune complexes by Clq and C3. Thus, we propose that the innate immune system controls both the frequency of peripheral, self-reactive B cells and their exposure to antigen.
Funding Period: 2001-03-15 - 2007-02-28
more information: NIH RePORT

Top Publications

  1. pmc Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow
    Yoshihiro Ueda
    Department of Immunology, Duke University, Durham, NC 27710, USA
    J Exp Med 201:1771-80. 2005
  2. pmc T-independent activation-induced cytidine deaminase expression, class-switch recombination, and antibody production by immature/transitional 1 B cells
    Yoshihiro Ueda
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 178:3593-601. 2007
  3. pmc Reduced infection in mosquitoes exposed to blood meals containing previously frozen flaviviruses
    Stephanie L Richards
    University of Florida, Institute of Food and Agricultural Sciences, Department of Entomology and Nematology, Florida Medical Entomology Laboratory, 200 9th St S E, Vero Beach, FL 32962, USA
    Virus Res 129:224-7. 2007
  4. pmc Impact of extrinsic incubation temperature and virus exposure on vector competence of Culex pipiens quinquefasciatus Say (Diptera: Culicidae) for West Nile virus
    Stephanie L Richards
    University of Florida, Institute of Food and Agricultural Sciences, Department of Entomology and Nematology, Florida Medical Entomology Laboratory, Vero Beach, Florida 32962, USA
    Vector Borne Zoonotic Dis 7:629-36. 2007
  5. pmc West Nile virus infection alters midgut gene expression in Culex pipiens quinquefasciatus Say (Diptera: Culicidae)
    Chelsea T Smartt
    University of Florida, Institute of Food and Agricultural Sciences, Florida Medical Entomology Laboratory, Vero Beach, Florida 32962, USA
    Am J Trop Med Hyg 81:258-63. 2009
  6. pmc Environmental and biological factors influencing Culex pipiens quinquefasciatus Say (Diptera: Culicidae) vector competence for Saint Louis encephalitis virus
    Stephanie L Richards
    Florida Medical Entomology Laboratory, University of Florida, Vero Beach, Florida 32962, USA
    Am J Trop Med Hyg 81:264-72. 2009

Scientific Experts

Detail Information

Publications6

  1. pmc Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow
    Yoshihiro Ueda
    Department of Immunology, Duke University, Durham, NC 27710, USA
    J Exp Med 201:1771-80. 2005
    ..We demonstrate that granulopoiesis and lymphopoiesis are coupled specifically in the bone marrow by development in a common niche and propose that the leukopoietic equilibrium is specified by limiting amounts of developmental resources...
  2. pmc T-independent activation-induced cytidine deaminase expression, class-switch recombination, and antibody production by immature/transitional 1 B cells
    Yoshihiro Ueda
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 178:3593-601. 2007
    ..We propose that inflammation-induced extramedullary lymphopoiesis represents a specialized mechanism for innate Ab responses to microbial pathogens...
  3. pmc Reduced infection in mosquitoes exposed to blood meals containing previously frozen flaviviruses
    Stephanie L Richards
    University of Florida, Institute of Food and Agricultural Sciences, Department of Entomology and Nematology, Florida Medical Entomology Laboratory, 200 9th St S E, Vero Beach, FL 32962, USA
    Virus Res 129:224-7. 2007
    ..Fresh viruses used in artificial feeding systems may be a viable alternative to the heavily regulated and expensive use of live animals...
  4. pmc Impact of extrinsic incubation temperature and virus exposure on vector competence of Culex pipiens quinquefasciatus Say (Diptera: Culicidae) for West Nile virus
    Stephanie L Richards
    University of Florida, Institute of Food and Agricultural Sciences, Department of Entomology and Nematology, Florida Medical Entomology Laboratory, Vero Beach, Florida 32962, USA
    Vector Borne Zoonotic Dis 7:629-36. 2007
    ..This relationship is likely complex and dependent on diverse interactions between factors such as incubation temperature and viremia, which should also be assessed for field populations...
  5. pmc West Nile virus infection alters midgut gene expression in Culex pipiens quinquefasciatus Say (Diptera: Culicidae)
    Chelsea T Smartt
    University of Florida, Institute of Food and Agricultural Sciences, Florida Medical Entomology Laboratory, Vero Beach, Florida 32962, USA
    Am J Trop Med Hyg 81:258-63. 2009
    ..This cDNA represents a mosquito gene that is an excellent candidate for interacting with WNV in Cx. p. quinquefasciatus and may play a role in disease transmission...
  6. pmc Environmental and biological factors influencing Culex pipiens quinquefasciatus Say (Diptera: Culicidae) vector competence for Saint Louis encephalitis virus
    Stephanie L Richards
    Florida Medical Entomology Laboratory, University of Florida, Vero Beach, Florida 32962, USA
    Am J Trop Med Hyg 81:264-72. 2009
    ....