Antigen-tethering proteins on follicular dendritic cells influence the affinity and diversity of germinal-center B cells

To optimally protect a host, the adaptive immune system must generate antibodies that bind the pathogen with high affinity, yet are diverse enough to protect against potential escape mutations. To generate these antibodies, B cells inside so-called germinal centers (GCs) compete for survival based on their ability to extract antigen from the surface of specialized presenting cells called follicular dendritic cells (FDCs). It is an open question whether a mechanism exists to actively regulate the selection pressure for increased affinity or diversity among GC B cells. Curiously, FDCs tether antigen via not one, but two classes of receptors, complement receptors (CRs) and an Fc γ receptor (Fc γ R), that differ qualitatively in their ligands, affinities, and expression kinetics. Here, we present a minimal biophysical model of this two-receptor antigen-presentation system which suggests that the presence of Fc γ R may act as a biophysical control knob to steer the relative affinity and diversity of GC B cells. Our model is consistent with experimental observations reporting low affinity but high diversity in the absence of Fc γ Rs on FDCs.