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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049326-05
Application #
6861711
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Ridge, John P
Project Start
2001-03-15
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2007-02-28
Support Year
5
Fiscal Year
2005
Total Cost
$308,000
Indirect Cost
Name
Duke University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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