GCselection

Maturation of antibody responses in microanatomical structures called germinal centers (GC) is essential for long-term immune protection after infection or vaccination. Affinity maturation of B cells in GC is often referred to as a Darwinian evolution process, relying on cycles of mutations in Ab coding genes followed by selection of cells expressing the “fittest” antibodies. While the mutation mechanisms have been described in details, our understanding of the molecular criteria used for selection are still incomplete. Indeed, the current concept of affinity-based selection is challenged by two facts: (i) a large proportion of B cells in GC express antibodies that have no detectable specificity for the foreign antigens that triggered the response (bystander cells); (ii) the selection mechanism applies pulling forces on the antibody-antigen bond, but resistance to force is hardly ever characterized when investigating affinity as a selection criterion. In the GCselection project, we propose to revisit and quantify the extent of affinity-based selection in GC responses, relying on original inter-disciplinary methods at the crossroads of immunology, bioinformatics, and biophysics. On the one hand, we will characterize bystander B cells and their precursors in GC to understand the selection criteria applied to those cells after infection and vaccination. On the other hand, we will study the imprint of mechanical forces on affinity-based selection in the GC. The GCselection project will challenge the textbook definition of affinity-based selection in antibody responses. Beyond methodological advances, we expect to demonstrate novel concepts in B cell immunology that will be useful for designing the next generation of vaccines.