The application proposes two hypotheses: that complement proteins are essential for concentrating antigen in germinal centers or that complement receptors transduce activating signals in B-cells. The approach to be taken is to establish genetic models of mice deficient in the key receptors for complement C3 and C4, i.e., CR1 (CD35) and CR2 (CD21). Preliminary results indicate that these mice have profound defects in antibody responses to T-cell dependent antigens.
Four specific aims are set out: (1) To characterize immune defects in Cr2 -/- mice using in vitro and in vivo assays; (2) To use mice deficient in CD21, CD35 or both, to establish the mechanism by which these receptors affect B-cell function; (3) To compare the localization of antigen in normal versus CR2 deficient mice; and (4) To generate mice expressing only CD21 or CD35 so that their individual functions can be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI039246-05
Application #
6169332
Study Section
Immunobiology Study Section (IMB)
Program Officer
Adams, Ken
Project Start
1996-07-01
Project End
2001-09-29
Budget Start
2000-07-01
Budget End
2001-09-29
Support Year
5
Fiscal Year
2000
Total Cost
$354,879
Indirect Cost
Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
115524410
City
Boston
State
MA
Country
United States
Zip Code
02115
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