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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Immunobiology Study Section (IMB)
Program Officer
Adams, Ken
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Immune Disease Institute, Inc.
United States
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Firl, Daniel J; Degn, Soren E; Padera, Timothy et al. (2018) Capturing change in clonal composition amongst single mouse germinal centers. Elife 7:
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