Mathijs Broeren

Foto Mathijs M.Broeren[at]radboudumc.nl
+31(0)24 3613686
Lab 6.15

 Detection and characterization of autoreactive B cells

My research focuses on the detection and characterization of B cells associated with autoimmunity. These B cells produce the antibodies responsible for a variety of diseases, like rheumatoid arthritis. At present, it is still not clear where in the body these cells are located and why our immune system fails to deplete these cells before they start to produce antibodies. In my research I focus on the B cells from patients with Sjögren’s Syndrome (SS), which is an autoimmune disease affecting exocrine glands, like the tear glands and salivary glands. There is no treatment available that interferes with the progression of the disease.

I am developing molecules to label the autoreactive B cells. B cells carry antibodies on their membrane, known as the B cell receptors (BCRs), which are used to sense the presence of target antigen as a trigger for cell activation. The BCR is unique for every B cell clone and therefore the ideal target to identify potentially autoreactive cells. This may be achieved by coupling antigen to an imaging label. However, it is known that the BCRs of autoreactive B cells have a particularly low affinity for their target antigen. I am therefore creating molecules with multiple autoantigens to increase the avidity for the autoreactive B cells.

The multimeric compounds are generally constructed using peptides that contain the targeted part of proteins, a (fluorescent) tag and a strategy to create multimers. Examples of constructs that we are using are streptavidin tetramers, elastin-like polypeptides (ELPs) and PLGAs. The final goal is to provide a molecule to label and track the autoreactive B cells in SS patients. This will enable the specific studying of the disease-associated cells and provide a means to track the effects B cell depletion therapies.

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