The immune system is continuously faced with the dilemma of distinguishing between self and non-self antigens. The complement system, a set of more than 20 serum proteins and receptors, is one of the critical components of the immune system involved in making this choice. Upon activation of the complement system in the peripheral tissues by a foreign antigen, complement components are covalently attached to the antigen. Complement receptors on dendritic cells (DCs) and follicular dendritic cells (FDCs) are then involved in the trafficking to, and presentation and retention of the antigen in the peripheral lymph nodes (LN).
The detailed microenvironment in the LN, where the antigen is presented to T and B cells, determines whether or not an immune response is mounted. While these general characteristics of antigen trafficking and presentation are widely accepted, the fundamental requirements for complement activation and its role in antigen trafficking have remained unclear. Furthermore, it has so far been impossible to address FDC biology in vivo.
In the current project I propose to visualize for the first time FDCs in vivo using novel techniques for intravital microscopy in an FDC-reporter mouse generated in the Carroll lab. I will generate reporter mice for complement factor 4 (C4). I will generate bone marrow chimeras from complement deficient mice, in the FDC- and C4-reporter mice and investigate the cellular source of complement, the location of complement conjugation to Ag, and the role of complement in t he transport of Ag to FDCs in secondary and tertiary lymphoid tissue upon intradermal exposure to Ag. My work will provide new insight into the processes of immune regulation and tolerance.
Field of science
- /natural sciences/biological sciences/microbiology
- /social sciences/social and economic geography/transport
- /medical and health sciences/health sciences/public and environmental health/epidemics prevention/immunisation
- /natural sciences/physical sciences/optics/microscopy
- /medical and health sciences/basic medicine/immunology
Call for proposal
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