Complement receptors CD21/CD35 provide an important link between innate and adaptive immunity by mediating the enhancing effects of complement on B cell activation and memory. On B cells CD21/CD35 form a co-receptor along with CD19 and CD81;whereas on follicular dendritic cells (FDC) they provide a mechanism for antigen retention. In both cases they serve to enhance the effects of antigen on the humoral response. The overall goal of this proposal is to clarify how complement receptors participate in the uptake, transport and deposition of antigen within the lymphoid compartment and to dissect the mechanism whereby they influence differentiation of activated B cells.
Three aims are proposed:
The first aim will examine the mechanism of uptake, transport and transfer of protein antigen onto FDC in peripheral lymph nodes.
The second aim will test the hypothesis that follicular B cells form a synapse with FDCin vitro and vivo and that co-receptor signaling participates in antigen uptake.
The third aim will test the hypothesis that the complement system participates in differentiation of GCB cells into antibody secreting cells (BASC) and memory Understanding how the complement system enhances trafficking and uptake of antigen within the lymphoid compartment and influences B cell differentiation into antibody secreting cells or memory cells is significant as it will not only extend our understanding of these processes but could be valuable in development of vaccination protocols.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI039246-14
Application #
7777377
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Dong, Gang
Project Start
1996-09-30
Project End
2011-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
14
Fiscal Year
2010
Total Cost
$495,090
Indirect Cost
Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
059709394
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Jafarnejad, Mohammad; Woodruff, Matthew C; Zawieja, David C et al. (2015) Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes. Lymphat Res Biol 13:234-47
Astarita, Jillian L; Cremasco, Viviana; Fu, Jianxin et al. (2015) The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nat Immunol 16:75-84
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
Heesters, Balthasar A; Myers, Riley C; Carroll, Michael C (2014) Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol 14:495-504
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
Heesters, Balthasar A; Das, Abhishek; Chatterjee, Priyadarshini et al. (2014) Do follicular dendritic cells regulate lupus-specific B cells? Mol Immunol 62:283-8
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
Chatterjee, Priyadarshini; Agyemang, Amma F; Alimzhanov, Marat B et al. (2013) Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner. Eur J Immunol 43:2441-2450

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