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.
| Firl, Daniel J; Degn, Soren E; Padera, Timothy et al. (2018) Capturing change in clonal composition amongst single mouse germinal centers. Elife 7: |
| 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 |
| 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 |
Showing the most recent 10 out of 34 publications
