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.
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|Degn, Søren E; van der Poel, Cees E; Firl, Daniel J et al. (2017) Clonal Evolution of Autoreactive Germinal Centers. Cell 170:913-926.e19|
|Heesters, Balthasar A; Carroll, Michael C (2016) The Role of Dendritic Cells in S. pneumoniae Transport to Follicular Dendritic Cells. Cell Rep 16:3130-3137|
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|Heesters, Balthasar A; Myers, Riley C; Carroll, Michael C (2014) Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol 14:495-504|
|Zhao, Fan; Heesters, Balthasar A; Chiu, Isaac et al. (2014) L-Rhamnose-containing supramolecular nanofibrils as potential immunosuppressive materials. Org Biomol Chem 12:6816-9|
|Dwyer, Daniel F; Woodruff, Matthew C; Carroll, Michael C et al. (2014) B cells regulate CD4+ T cell responses to papain following B cell receptor-independent papain uptake. J Immunol 193:529-39|
|Woodruff, Matthew C; Heesters, Balthasar A; Herndon, Caroline N et al. (2014) Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine. J Exp Med 211:1611-21|
|Heesters, Balthasar A; Das, Abhishek; Chatterjee, Priyadarshini et al. (2014) Do follicular dendritic cells regulate lupus-specific B cells? Mol Immunol 62:283-8|
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