Germinal center mechanics
Our work in this area focuses on germinal centers as "evolution machines" that take as an input low-affinity B cells and output high-affinity ones. How does this evolutionary process work? At the cellular level, how do B cells "know" when they make higher affinity antibodies than there neighbors? How much of this is intrinsic to the B cell, and how much depends on other cells like T follicular helpers? At the molecular level, how do the signals that higher affinity B cells receive allow them to undergo the proliferative bursts that lead to their enrichment in the population?
One of the current models for germinal center selection proposes that higher affinity B cells can retrieve and present more antigen to germinal center-resident T follicular helper (Tfh) cells, which then drive B cell proliferation. This places special emphasis on the dynamics of the Tfh cells themselves as a driving force in the germinal center. We study different aspects of Tfh biology, including their clonal and migratory dynamics and their cellular and molecular biology.
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B cell clonal dynamics
In addition generating high-affinity antibodies through affinity maturation, GCs, and the B cell system in general, also serve as "filters" that ultimately determine the diversity and fine specificity of the antibody pool in serum. We study how competition between B cell clones shapes the resulting antibody pool in various different conditions ranging from viral infection to the response to bacterial commensals in the gut. We hope to contribute to the understanding of vaccine-relevant phenomena such as immunodominance, antibody imprinting, and the ominously-named "original antigenic sin."
interactions in vivo
We developed LIPSTIC (Labeling of Immune Partnerships by SorTagging Intercellular Contacts), a method to study cell-cell interactions in vivo based on enzymatic transfer of labeled substrates from one cell to another. Almost like real lipstick, made to track cellular kiss-and-run events. We apply LIPSTIC to all sorts of mouse models, from germinal centers and cancer immunology to the priming of gut T cell responses.